Hypertriglyceridemia (HTG) is a feature of numerous metabolic disorders including dyslipidemias, metabolic syndrome, and diabetes mellitus type 2 and can increase the risk of premature coronary artery disease. HTG may also be due to genetic factors (called primary HTG) and particularly the severe/extreme HTG (SEHTG), which is a usually rare genetic disorder. Even rarer are secondary cases of SEHTG caused by autoimmune disease. This review considers the causes of SEHTG, and their management including treatment with low density lipoprotein apheresis and analyzes the original findings.

Olga Diakoumakou

Georgios Hatzigeorgiou

Nikos Gontoras

Maria Boutsikou

Vana Kolovou

Sophie Mavrogeni

Vassiliki Giannakopoulou

Genovefa D. Kolovou

Severe/Extreme Hypertriglyceridemia and LDL Apheretic Treatment: Review of the Literature, Original Findings

Statins are the most widely prescribed and effective medication for reducing low density lipoprotein cholesterol.  Statins may also lower resting blood pressure (BP); however, results are inconsistent. We sought to determine if the maximum dose of atorvastatin reduces resting BP and the peak systolic BP (SBP) achieved on a graded exercise stress test (GEST) among a large sample of 419 healthy men (48&#x25;) and women (52&#x25;). Subjects (419, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.3625803pt" id="M1" height="9.06134pt" version="1.1" viewBox="-0.0498162 -8.69876 52.9769 9.06134" width="52.9769pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g113-53" d="M456 178V225H360V632H320C217 496 115 347 20 206V178H280V106C280 40 276 34 189 27V0H445V27C364 34 360 39 360 106V178H456ZM280 225H82C149 335 214 431 278 520H280V225Z"/></g><g transform="matrix(.0135,0,0,-0.0135,6.503,0)"><use xlink:href="#g113-53"/></g><g transform="matrix(.0135,0,0,-0.0135,13.007,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.0135,0,0,-0.0135,16.096,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g><g transform="matrix(.0135,0,0,-0.0135,25.627,0)"><path id="g117-37" d="M535 290V340H323V533H265V340H52V290H265V84H323V290H535ZM535 -22V28H52V-22H535Z"/></g><g transform="matrix(.0135,0,0,-0.0135,36.608,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.0135,0,0,-0.0135,43.111,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,46.2,0)"><path id="g113-57" d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"/></g></svg>&#x2009;yr) were double-blinded and randomized to 80&#x2009;mg<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.04981995pt" id="M2" height="4.3561pt" version="1.1" viewBox="-0.0498162 -4.30628 3.20019 4.3561" width="3.20019pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g113-46" d="M170 255C170 288 146 313 114 313S58 288 58 255C58 221 82 198 114 198S170 221 170 255Z"/></g></svg>d<sup>&#x2212;1</sup> of atorvastatin (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2130003pt" id="M3" height="8.91176pt" version="1.1" viewBox="-0.0498162 -8.69876 42.0615 8.91176" width="42.0615pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g113-111" d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z"/></g><g transform="matrix(.0135,0,0,-0.0135,10.586,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g><g transform="matrix(.0135,0,0,-0.0135,22.324,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g><g transform="matrix(.0135,0,0,-0.0135,28.827,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,35.33,0)"><use xlink:href="#g113-51"/></g></svg>) or placebo (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2130003pt" id="M4" height="8.91176pt" version="1.1" viewBox="-0.0498162 -8.69876 42.0615 8.91176" width="42.0615pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-111"/></g><g transform="matrix(.0135,0,0,-0.0135,10.586,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.0135,0,0,-0.0135,22.324,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.0135,0,0,-0.0135,28.827,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.0135,0,0,-0.0135,35.33,0)"><path id="g113-56" d="M447 623H65C61 580 56 530 47 475H76C100 541 106 550 172 550H388C308 376 196 170 91 -1L98 -12L172 -2C268 204 360 408 455 611L447 623Z"/></g></svg>) for 6&#x2009;mo. Among the total sample, there were no differences in resting BP (SBP, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2129908pt" id="M5" height="9.21094pt" version="1.1" viewBox="-0.0498162 -8.99795 46.7259 9.21094" width="46.7259pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><path id="g113-52" d="M285 378C315 398 338 416 353 432C373 451 384 474 384 503C384 579 325 635 236 635H235C182 635 136 610 108 579L65 516L85 496C110 533 150 575 205 575C258 575 300 543 300 481C300 407 232 369 141 339L147 310C163 315 188 321 211 321C268 321 338 284 338 192C338 94 288 40 217 40C160 40 119 68 93 91C85 98 77 97 69 91C60 84 47 71 46 58C44 46 48 35 62 22C75 10 116 -12 162 -12C234 -12 424 62 424 224C424 297 373 359 285 376V378Z"/></g><g transform="matrix(.0135,0,0,-0.0135,39.983,0)"><use xlink:href="#g113-49"/></g></svg>; diastolic BP [DBP], <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2129908pt" id="M6" height="9.21094pt" version="1.1" viewBox="-0.0498162 -8.99795 46.7259 9.21094" width="46.7259pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><path id="g113-55" d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z"/></g><g transform="matrix(.0135,0,0,-0.0135,39.983,0)"><path id="g113-58" d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z"/></g></svg>; mean arterial pressure (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2129908pt" id="M7" height="9.21094pt" version="1.1" viewBox="-0.0498162 -8.99795 46.7259 9.21094" width="46.7259pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><use xlink:href="#g113-56"/></g><g transform="matrix(.0135,0,0,-0.0135,39.985,0)"><use xlink:href="#g113-55"/></g></svg>); or peak SBP on a GEST (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2129908pt" id="M8" height="9.21094pt" version="1.1" viewBox="-0.0498162 -8.99795 46.7259 9.21094" width="46.7259pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><use xlink:href="#g113-58"/></g><g transform="matrix(.0135,0,0,-0.0135,39.984,0)"><use xlink:href="#g113-58"/></g></svg>)) over 6&#x2009;mo, regardless of drug treatment group.  However, among women on atorvastatin, resting SBP/DBP (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.3625803pt" id="M9" height="9.06134pt" version="1.1" viewBox="-0.0498162 -8.69876 46.4494 9.06134" width="46.4494pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-52"/></g><g transform="matrix(.0135,0,0,-0.0135,6.503,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,9.592,0)"><use xlink:href="#g113-56"/></g><g transform="matrix(.0135,0,0,-0.0135,19.126,0)"><use xlink:href="#g117-37"/></g><g transform="matrix(.0135,0,0,-0.0135,30.107,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.0135,0,0,-0.0135,36.61,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,39.699,0)"><path id="g113-54" d="M153 550H386L412 615L406 623H120L82 318C104 327 142 338 184 338C294 338 347 275 347 187C347 112 305 39 221 39C160 39 119 71 97 89C88 97 80 96 71 90C59 80 50 67 49 57C48 45 52 36 66 23C80 9 123 -12 169 -12C221 -11 288 15 342 59C403 109 431 165 431 225C431 308 366 395 238 395C212 395 165 379 127 364L153 550Z"/></g></svg>&#x2009;mmHg, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-2.2392pt" id="M10" height="11.9171pt" version="1.1" viewBox="-0.0498162 -9.6779 98.6784 11.9171" width="98.6784pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,39.983,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.0135,0,0,-0.0135,46.486,0)"><path id="g113-48" d="M368 703H309L44 -163H104L368 703Z"/></g><g transform="matrix(.0135,0,0,-0.0135,52.073,0)"><use xlink:href="#g113-52"/></g><g transform="matrix(.0135,0,0,-0.0135,58.576,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,61.665,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.0135,0,0,-0.0135,71.196,0)"><use xlink:href="#g117-37"/></g><g transform="matrix(.0135,0,0,-0.0135,82.177,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,88.68,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,91.769,0)"><use xlink:href="#g113-58"/></g></svg>&#x2009;mmHg, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2129908pt" id="M11" height="9.21094pt" version="1.1" viewBox="-0.0498162 -8.99795 46.7259 9.21094" width="46.7259pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,39.983,0)"><use xlink:href="#g113-51"/></g></svg>) and peak SBP on a GEST (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.3625803pt" id="M12" height="9.06134pt" version="1.1" viewBox="-0.0498162 -8.69876 46.4494 9.06134" width="46.4494pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-55"/></g><g transform="matrix(.0135,0,0,-0.0135,6.503,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,9.592,0)"><use xlink:href="#g113-54"/></g><g transform="matrix(.0135,0,0,-0.0135,19.124,0)"><use xlink:href="#g117-37"/></g><g transform="matrix(.0135,0,0,-0.0135,30.105,0)"><use xlink:href="#g113-50"/></g><g transform="matrix(.0135,0,0,-0.0135,36.608,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,39.697,0)"><use xlink:href="#g113-54"/></g></svg>&#x2009;mmHg, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2129908pt" id="M13" height="9.21094pt" version="1.1" viewBox="-0.0498162 -8.99795 46.7259 9.21094" width="46.7259pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,39.983,0)"><use xlink:href="#g113-53"/></g></svg>) were lower versus men. Atorvastatin lowered resting BP 3-4&#x2009;mmHg and peak SBP on a GEST &#x7e;7&#x2009;mmHg more among women than men over 6&#x2009;mo of treatment. The inconsistent findings regarding the antihypertensive effects of statins may be partially explained by not accounting for sex effects.

Amanda L. Zaleski

Marianne L. Mentch

Linda S. Pescatello

Beth A. Taylor

Jeffrey A. Capizzi

Adam S. Grimaldi

Priscilla M. Clarkson

Stephanie A. Moeckel-Cole

Stuart R. Chipkin

Justin Keadle

Charles Michael White

Paul D. Thompson

Effects of Atorvastatin on Resting and Peak Exercise Blood Pressure among Normotensive Men and Women

Increasing evidence suggests that erythrocytes may participate in atherogenesis. We sought to investigate whether the total cholesterol content of erythrocyte membranes (CEM) is significantly different in patients with stable coronary artery disease (CAD) compared to patients with nonsignificant coronary stenosis and determine the correlation between CEM and the severity of coronary stenosis. <i>Methods</i>. The population included 144 patients, undergoing clinically indicated coronary angiography. The severity of coronary stenosis was scored after coronary angiography and patients were divided into two groups; the <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2129908pt" id="M1" height="9.21094pt" version="1.1" viewBox="-0.0498162 -8.99795 6.51834 9.21094" width="6.51834pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g113-84" d="M449 634C442 637 425 643 405 650C376 660 341 666 307 666C181 666 98 590 98 485C98 400 170 343 215 310L246 288C307 243 343 204 343 147C343 67 291 18 219 18C104 18 61 124 51 202L23 199C28 124 27 71 27 47C47 22 122 -16 204 -16C324 -16 428 60 428 174C428 256 379 309 307 360L276 382C223 419 179 455 179 516C179 576 221 632 293 632C379 632 410 564 418 487L448 490C446 536 446 592 449 634Z"/></g></svg>-stenosis group (CAD patients, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2130003pt" id="M2" height="8.91176pt" version="1.1" viewBox="-0.0498162 -8.69876 35.534 8.91176" width="35.534pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g113-111" d="M495 86L479 114C446 82 419 66 409 66C401 66 401 72 406 97C420 166 436 231 453 297C489 435 454 448 428 448C406 448 384 439 354 422C305 394 222 327 161 247H159L183 345C200 415 194 448 173 448C143 448 82 410 23 351L38 325C64 349 95 371 105 371C111 371 116 365 109 336L25 -4L31 -12C50 -4 77 3 107 9C119 69 132 122 145 168C197 254 321 381 370 381C387 381 393 374 378 305L329 95C309 17 320 -12 345 -12C372 -12 430 19 495 86Z"/></g><g transform="matrix(.0135,0,0,-0.0135,10.586,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g><g transform="matrix(.0135,0,0,-0.0135,22.324,0)"><path id="g113-57" d="M249 635C141 635 70 555 70 471C70 401 114 353 179 316C143 294 106 267 90 252C68 231 45 202 45 157C45 50 130 -12 237 -12C322 -12 435 52 435 169C435 256 372 304 303 343C349 374 375 398 383 407C401 429 411 458 411 487C411 569 344 635 249 635ZM238 603C285 603 337 567 337 482C337 422 310 385 276 358C205 393 145 426 145 500C145 552 179 603 238 603ZM248 20C183 20 125 70 125 163C125 218 158 268 206 300C284 261 355 217 355 143C355 66 308 20 248 20Z"/></g><g transform="matrix(.0135,0,0,-0.0135,28.827,0)"><path id="g113-51" d="M412 140C382 77 369 73 315 73H129L270 222C362 320 402 379 402 466C402 571 322 635 234 635C177 635 130 609 99 576L42 495L64 475C90 514 133 568 201 568C274 568 318 519 318 435C318 349 255 267 193 193C144 135 87 78 32 23V0H405C417 45 427 89 440 131L412 140Z"/></g></svg>) had a significant stenosis indicated by coronary angiography and the second group, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2129908pt" id="M3" height="9.21094pt" version="1.1" viewBox="-0.0498162 -8.99795 11.5092 9.21094" width="11.5092pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g113-79" d="M822 650H589L583 622C660 617 677 607 674 561C672 534 664 481 647 390L600 137H596L273 650H126L120 622C176 620 194 615 207 594C221 571 225 557 214 504L161 257C141 166 129 112 121 85C108 42 83 30 29 28L23 0H260L266 28C193 33 173 42 176 89C178 122 186 172 202 255L256 527H259L583 -8H612L690 390C708 481 720 535 728 558C744 603 756 619 816 622L822 650Z"/></g></svg>-stenosis (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2130003pt" id="M4" height="8.91176pt" version="1.1" viewBox="-0.0498162 -8.69876 35.534 8.91176" width="35.534pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-111"/></g><g transform="matrix(.0135,0,0,-0.0135,10.586,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.0135,0,0,-0.0135,22.324,0)"><path id="g113-55" d="M137 343C167 482 260 545 321 574C357 591 397 603 429 609L423 641C382 634 335 622 295 608C189 570 37 457 37 238C37 84 125 -12 242 -12C362 -12 447 89 447 209C447 311 374 393 267 393C247 393 226 386 204 376L137 343ZM227 337C318 337 361 256 361 173C361 105 336 22 258 22C176 22 126 120 126 240C126 266 127 291 132 310C155 323 189 337 227 337Z"/></g><g transform="matrix(.0135,0,0,-0.0135,28.828,0)"><use xlink:href="#g113-51"/></g></svg>), had nonsignificant coronary stenosis. Lipid parameters were determined by routine laboratory methods. CEM was measured using an enzymatic assay, and protein content was assessed by the modified Lowry method. <i>Results.</i> The mean of CEM levels was higher (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.6617603pt" id="M5" height="9.65971pt" version="1.1" viewBox="-0.0498162 -8.99795 53.2534 9.65971" width="53.2534pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g113-81" d="M600 480C600 590 528 650 384 650H143L137 622C222 614 225 607 210 531L130 127C113 41 106 36 23 28L17 0H294L300 28C204 36 195 42 212 127L243 284L314 263C327 263 339 263 352 264C465 271 600 337 600 480ZM508 481C508 351 402 304 329 304C289 304 265 311 250 317L295 559C302 594 310 606 323 611C335 616 350 619 367 619C455 619 508 573 508 481Z"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><path id="g113-49" d="M241 635C89 635 35 457 35 312C35 153 89 -12 240 -12C390 -12 443 166 443 312C443 466 390 635 241 635ZM238 602C329 602 354 454 354 312C354 172 330 22 240 22C152 22 124 173 124 313S148 602 238 602Z"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><path id="g113-47" d="M113 -12C146 -12 170 11 170 46C170 78 146 103 114 103S58 78 58 46C58 11 82 -12 113 -12Z"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,39.983,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,46.486,0)"><path id="g113-50" d="M384 0V27C293 34 287 42 287 114V635C232 613 172 594 109 583V559L157 557C201 555 205 550 205 499V114C205 42 199 34 109 27V0H384Z"/></g></svg>) in stable CAD patients (137.2&#x2009;<i>&#xb5;</i>g/mg of membrane protein) compared with <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2129908pt" id="M6" height="9.21094pt" version="1.1" viewBox="-0.0498162 -8.99795 11.5092 9.21094" width="11.5092pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-79"/></g></svg>-stenosis patients (110.0&#x2009;<i>&#xb5;</i>g/mg of membrane protein). The coronary artery scores were correlated positively with CEM levels (<svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2130003pt" id="M7" height="8.91176pt" version="1.1" viewBox="-0.0498162 -8.69876 50.6016 8.91176" width="50.6016pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><path id="g113-115" d="M393 379C402 394 400 411 393 422C384 437 365 448 348 448C301 448 237 372 186 285H182L193 335C210 408 205 448 178 448C150 448 80 402 29 344L45 321C80 355 114 373 122 373C128 373 130 365 124 330C106 228 76 98 50 -5L57 -12C82 -5 112 3 132 6L172 203C196 256 234 304 254 329C275 355 293 367 306 367C318 367 330 360 342 348C347 343 355 343 365 350S386 367 393 379Z"/></g><g transform="matrix(.0135,0,0,-0.0135,9.505,0)"><use xlink:href="#g117-34"/></g><g transform="matrix(.0135,0,0,-0.0135,21.242,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,27.746,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,30.834,0)"><use xlink:href="#g113-51"/></g><g transform="matrix(.0135,0,0,-0.0135,37.338,0)"><path id="g113-58" d="M244 635C114 635 38 519 38 422C38 317 111 240 217 240C236 240 255 244 277 256L345 292C311 140 203 39 59 15L64 -15C89 -15 150 -5 204 17C339 72 440 202 440 386C440 521 368 635 244 635ZM228 602C326 602 352 479 352 390C352 370 351 347 348 324C327 308 293 296 258 296C174 296 124 369 124 458C124 517 152 602 228 602Z"/></g><g transform="matrix(.0135,0,0,-0.0135,43.842,0)"><use xlink:href="#g113-55"/></g></svg>, <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.6617603pt" id="M8" height="9.65971pt" version="1.1" viewBox="-0.0498162 -8.99795 53.2534 9.65971" width="53.2534pt"><g transform="matrix(.0135,0,0,-0.0135,0,0)"><use xlink:href="#g113-81"/></g><g transform="matrix(.0135,0,0,-0.0135,12.15,0)"><use xlink:href="#g117-91"/></g><g transform="matrix(.0135,0,0,-0.0135,23.887,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,30.39,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.0135,0,0,-0.0135,33.48,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,39.983,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.0135,0,0,-0.0135,46.486,0)"><use xlink:href="#g113-50"/></g></svg>). <i>Conclusion</i>. CEM levels are positively associated with the severity of CAD, meaning that CEM might contribute to the development of CAD.

Gholamreza Namazi

Morteza Pourfarzam

Sabieh Jamshidi Rad

Ahmad Movahedian Attar

Nizal Sarrafzadegan

Masoumeh Sadeghi

Parastoo Asa

Association of the Total Cholesterol Content of Erythrocyte Membranes with the Severity of Disease in Stable Coronary Artery Disease

Disease phenotypes and defects in function can be traced to nonsynonymous single nucleotide polymorphisms (nsSNPs), which are important indicators of action sites and effective potential therapeutic approaches. Identification of deleterious nsSNPs is crucial to characterize the genetic basis of diseases, assess individual susceptibility to disease, determinate molecular and therapeutic targets, and predict clinical phenotypes. In this study using PolyPhen2 and MutPred in silico algorithms, we analyzed the genetic variations that can alter the expression and function of the ABCA1 gene that causes the allelic disorders familial hypoalphalipoproteinemia and Tangier disease. Predictions were validated with published results from <i>in vitro, in vivo</i>, and human studies. Out of a total of 233 nsSNPs, 80 (34.33&#x25;) were found deleterious by both methods. Among these 80 deleterious nsSNPs found, 29 (12.44&#x25;) rare variants resulted highly deleterious with a probability &#x3E;0.8. We have observed that mostly variants with verified functional effect in experimental studies are correctly predicted as damage variants by MutPred and PolyPhen2 tools. Still, the controversial results of experimental approaches correspond to nsSNPs predicted as neutral by both methods, or contradictory predictions are obtained for them.  A total of seventeen nsSNPs were predicted as deleterious by PolyPhen2, which resulted neutral by MutPred. Otherwise, forty two nsSNPs were predicted as deleterious by MutPred, which resulted neutral by PolyPhen2.

Francisco R. Mar&#xed;n-Mart&#xed;n

Cristina Soler-Rivas

Roberto Mart&#xed;n-Hern&#xe1;ndez

Arantxa Rodriguez-Casado

A Comprehensive In Silico Analysis of the Functional and Structural Impact of Nonsynonymous SNPs in the ABCA1 Transporter Gene

Diabetes mellitus is associated with dysregulation of adipose tissue metabolism and increased level of serum lipids. In our previous work we found that <i>Securigera securidaca</i> decreases cholesterol level in blood of diabetic rats. The present study was carried out to further investigate the effects of this plant on lipid metabolism, lipolysis, and adipogenesis, in diabetic rats. Female Wistar rats were rendered diabetic by intraperitoneal injection of streptozotocin. Retroperitoneal adipose tissue was removed from diabetic animals after seven days of streptozotocin injection. Effect of hydroalcoholic extract of <i>S. securidaca</i> seeds (100–800 <i>μ</i>g/mL) on adipose tissue lipolysis was evaluated in <i>ex vivo</i> condition. Also, to evaluate adipogenesis, preadipocytes were isolated from adipose tissue and differentiated to adipocytes in the presence of the extract. The extract at concentration of 800 <i>μ</i>g/mL decreased both basal and catecholamine-stimulated lipolysis <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-2.21957pt;width:70.474998px;" id="M1" height="15.0875" version="1.1" viewBox="0 0 70.474998 15.0875" width="70.474998">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,12.138)"><path id="x28" d="M300 -147l-18 -23q-106 71 -159 185.5t-53 254.5v1q0 139 53 252.5t159 186.5l18 -24q-74 -62 -115.5 -173.5t-41.5 -242.5q0 -130 41.5 -242.5t115.5 -174.5z"></path></g><g transform="matrix(.017,-0,0,-.017,5.944,12.138)"><path id="x1D443" d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5&#xA;t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z"></path></g><g transform="matrix(.017,-0,0,-.017,21.464,12.138)"><path id="x3C" d="M512 -3l-437 233v51l437 233v-58l-378 -200v-2l378 -199v-58z"></path></g><g transform="matrix(.017,-0,0,-.017,36.168,12.138)"><path id="x30" d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105&#xA;q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z"></path></g><g transform="matrix(.017,-0,0,-.017,44.327,12.138)"><path id="x2E" d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z"></path></g><g transform="matrix(.017,-0,0,-.017,48.203,12.138)"><use xlink:href="#x30"></use></g><g transform="matrix(.017,-0,0,-.017,56.362,12.138)"><path id="x35" d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8&#xA;l-26 -65h-233z"></path></g><g transform="matrix(.017,-0,0,-.017,64.522,12.138)"><path id="x29" d="M275 270q0 -296 -211 -440l-19 23q75 62 116.5 174t41.5 243t-42 243t-116 173l19 24q211 -144 211 -440z"></path></g>

		
	
</svg>. Incubation of differentiating preadipocytes with 800 <i>μ</i>g/mL of <i>S. securidaca</i> extract decreased intracellular lipid droplet accumulation as evaluated with Oil Red O staining <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-2.21957pt;width:78.637497px;" id="M2" height="15.0875" version="1.1" viewBox="0 0 78.637497 15.0875" width="78.637497">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,12.138)"><use xlink:href="#x28"></use></g><g transform="matrix(.017,-0,0,-.017,5.944,12.138)"><use xlink:href="#x1D443"></use></g><g transform="matrix(.017,-0,0,-.017,21.464,12.138)"><use xlink:href="#x3C"></use></g><g transform="matrix(.017,-0,0,-.017,36.168,12.138)"><use xlink:href="#x30"></use></g><g transform="matrix(.017,-0,0,-.017,44.327,12.138)"><use xlink:href="#x2E"></use></g><g transform="matrix(.017,-0,0,-.017,48.203,12.138)"><use xlink:href="#x30"></use></g><g transform="matrix(.017,-0,0,-.017,56.362,12.138)"><use xlink:href="#x30"></use></g><g transform="matrix(.017,-0,0,-.017,64.522,12.138)"><path id="x31" d="M384 0h-275v27q67 5 81.5 18.5t14.5 68.5v385q0 38 -7.5 47.5t-40.5 10.5l-48 2v24q85 15 178 52v-521q0 -55 14.5 -68.5t82.5 -18.5v-27z"></path></g><g transform="matrix(.017,-0,0,-.017,72.681,12.138)"><use xlink:href="#x29"></use></g>

		
	
</svg>. The extract even at high concentrations had no effect on viability of preadipocytes. In conclusion, <i>S. securidaca</i> decreases lipolysis and adipogenesis without cytotoxicity, which makes it a good candidate for management of dyslipidemia and reduction of cardiovascular risks in diabetes.

Ahmad Ghorbani

Reyhaneh Moradi Marjaneh

Ziba Rajaei

Mousa-Al-Reza Hadjzadeh

Effects of <i>Securigera securidaca</i> Extract on Lipolysis and Adipogenesis in Diabetic Rats

Currently, the Friedewald formula (FF) is the main method for evaluating low-density lipoprotein cholesterol (LDL-c). Recently, many limitations have emerged regarding its use, including patients with triglyceride levels &#x2265;400&#x2009;mg/dL, diabetes mellitus, and kidney or hepatic chronic diseases. We analyzed the use of the FF in patients with metabolic syndrome. We selected patients with known metabolic syndrome that fulfilled the <i  >National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report</i> and excluded patients with triglyceride levels &#x2265;400&#x2009;mg/dL and chronic liver and/or kidney disease. Using direct assays, we measured total cholesterol, high-density lipoprotein cholesterol, triglycerides, and LDL-c. Then, LDL-c was estimated using the FF and compared with the LDL-c by direct assay. The sample size was 135 patients. Using the FF, the mean LDL-c value was <svg     style="vertical-align:-0.3003pt;width:82.525002px;" id="M1" height="11.2875" version="1.1" viewBox="0 0 82.525002 11.2875" width="82.525002"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,10.862)"><path id="x31" d="M384 0h-275v27q67 5 81.5 18.5t14.5 68.5v385q0 38 -7.5 47.5t-40.5 10.5l-48 2v24q85 15 178 52v-521q0 -55 14.5 -68.5t82.5 -18.5v-27z" /></g><g transform="matrix(.017,-0,0,-.017,8.222,10.862)"><path id="x32" d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" /></g><g transform="matrix(.017,-0,0,-.017,16.381,10.862)"><path id="x34" d="M456 178h-96v-72q0 -51 12.5 -62.5t72.5 -16.5v-27h-256v27q65 5 78 17t13 62v72h-260v28q182 271 300 426h40v-407h96v-47zM280 225v295h-2q-107 -148 -196 -295h198z" /></g><g transform="matrix(.017,-0,0,-.017,24.541,10.862)"><path id="x2E" d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" /></g><g transform="matrix(.017,-0,0,-.017,28.416,10.862)"><use xlink:href="#x34"/></g><g transform="matrix(.017,-0,0,-.017,40.35,10.862)"><path id="xB1" d="M535 290h-212v-206h-58v206h-213v50h213v193h58v-193h212v-50zM535 -22h-483v50h483v-50z" /></g><g transform="matrix(.017,-0,0,-.017,54.102,10.862)"><use xlink:href="#x34"/></g><g transform="matrix(.017,-0,0,-.017,62.261,10.862)"><use xlink:href="#x32"/></g><g transform="matrix(.017,-0,0,-.017,70.42,10.862)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,74.296,10.862)"><use xlink:href="#x31"/></g>

		
	
</svg>&#x2009;mg/dL; it was <svg     style="vertical-align:-0.3003pt;width:82.525002px;" id="M2" height="11.2875" version="1.1" viewBox="0 0 82.525002 11.2875" width="82.525002"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,10.862)"><use xlink:href="#x31"/></g><g transform="matrix(.017,-0,0,-.017,8.222,10.862)"><use xlink:href="#x32"/></g><g transform="matrix(.017,-0,0,-.017,16.381,10.862)"><path id="x35" d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8&#xA;l-26 -65h-233z" /></g><g transform="matrix(.017,-0,0,-.017,24.541,10.862)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,28.416,10.862)"><use xlink:href="#x31"/></g><g transform="matrix(.017,-0,0,-.017,40.35,10.862)"><use xlink:href="#xB1"/></g><g transform="matrix(.017,-0,0,-.017,54.102,10.862)"><path id="x33" d="M285 378v-2q65 -13 102 -54.5t37 -97.5q0 -57 -30.5 -104.5t-74 -75t-85.5 -42t-72 -14.5q-31 0 -59.5 11t-40.5 23q-19 18 -16 36q1 16 23 33q13 10 24 0q58 -51 124 -51q55 0 88 40t33 112q0 64 -39 96.5t-88 32.5q-29 0 -64 -11l-6 29q77 25 118 57.5t41 84.5&#xA;q0 45 -26.5 69.5t-68.5 24.5q-67 0 -120 -79l-20 20l43 63q51 56 127 56h1q66 0 107 -37t41 -95q0 -42 -31 -71q-22 -23 -68 -54z" /></g><g transform="matrix(.017,-0,0,-.017,62.261,10.862)"><path id="x38" d="M249 635q70 0 116 -43t46 -105q0 -46 -28 -80q-22 -25 -80 -64q62 -35 97 -75t35 -99q0 -81 -63 -131t-135 -50q-83 0 -137.5 45.5t-54.5 123.5q0 52 45 95q29 28 89 64q-109 62 -109 155q0 66 50.5 115t128.5 49zM238 603q-42 0 -67.5 -31t-25.5 -72q0 -50 32.5 -79.5&#xA;t98.5 -62.5q61 48 61 124q0 59 -29.5 90t-69.5 31zM248 20q46 0 76.5 33.5t30.5 89.5q0 50 -39 85.5t-110 71.5q-81 -54 -81 -137q0 -67 35.5 -105t87.5 -38z" /></g><g transform="matrix(.017,-0,0,-.017,70.42,10.862)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,74.296,10.862)"><use xlink:href="#x35"/></g>

		
	
</svg>&#x2009;mg/dL by direct assay. The correlation coefficient between these two methods was 0.89, with statistical significance <svg     style="vertical-align:-2.3205pt;width:120.0625px;" id="M3" height="15.1125" version="1.1" viewBox="0 0 120.0625 15.1125" width="120.0625"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,12.162)"><path id="x28" d="M300 -147l-18 -23q-106 71 -159 185.5t-53 254.5v1q0 139 53 252.5t159 186.5l18 -24q-74 -62 -115.5 -173.5t-41.5 -242.5q0 -130 41.5 -242.5t115.5 -174.5z" /></g><g transform="matrix(.017,-0,0,-.017,5.944,12.162)"><path id="x1D443" d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5&#xA;t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" /></g><g transform="matrix(.017,-0,0,-.017,22.416,12.162)"><path id="x76" d="M478 437v-26q-39 -5 -53 -17.5t-35 -57.5q-68 -149 -142 -347h-28q-47 128 -138 350q-17 43 -30.5 54.5t-53.5 17.5v26h205v-26q-40 -4 -46.5 -14.5t6.5 -42.5q41 -115 95 -247q43 101 89 238q12 36 3.5 48.5t-50.5 17.5v26h178z" /></g><g transform="matrix(.017,-0,0,-.017,30.286,12.162)"><path id="x61" d="M433 39l-85 -51q-27 0 -47 20q-16 16 -24 44q-5 -3 -24 -16.5t-27 -18.5t-23 -13.5t-25 -12t-19 -3.5q-52 0 -86 36.5t-34 85.5q0 71 81 99q128 43 155 65v17q0 54 -23 83.5t-62 29.5q-28 0 -45 -19t-29 -66q-7 -23 -29 -23q-15 0 -29 13t-14 30t31 40q25 19 68.5 40.5&#xA;t81.5 29.5q49 0 82 -27q45 -39 45 -123v-185q0 -60 35 -60q18 0 36 11zM275 84v156q-12 -6 -49 -23t-41 -19q-31 -14 -46 -31t-15 -43q0 -35 22.5 -55.5t48.5 -20.5q19 0 42 10.5t38 25.5z" /></g><g transform="matrix(.017,-0,0,-.017,37.834,12.162)"><path id="x6C" d="M238 0h-223v26q48 5 60 17t12 61v473q0 50 -10.5 60.5t-58.5 15.5v24q73 8 148 35v-608q0 -49 11.5 -61t60.5 -17v-26z" /></g><g transform="matrix(.017,-0,0,-.017,41.947,12.162)"><path id="x75" d="M518 50v-26q-32 -4 -77 -16l-37 -11t-33 -9l-6 6v71q-56 -42 -74 -52q-43 -25 -77 -25q-55 0 -89.5 36.5t-34.5 112.5v196q0 38 -6.5 48.5t-26.5 15.5l-28 6v23q19 1 72 7q59 9 71 11q-3 -31 -3 -145v-135q0 -113 88 -113q59 0 108 48v234q0 38 -8 49t-34 15l-36 6v23&#xA;q44 2 90 8q37 4 67 10v-334q0 -37 8.5 -47t38.5 -12z" /></g><g transform="matrix(.017,-0,0,-.017,50.974,12.162)"><path id="x65" d="M380 106l15 -22q-42 -52 -87 -74t-76 -22q-89 0 -142 62t-53 151q0 103 66 175q67 73 146 73h1q61 0 105.5 -46.5t44.5 -105.5q0 -16 -4.5 -22.5t-18.5 -9.5q-54 -10 -262 -17q1 -95 46 -143.5t104 -48.5q61 0 115 50zM225 412q-35 0 -64.5 -32.5t-40.5 -90.5q83 0 170 3&#xA;q14 0 19 4.5t5 15.5q1 41 -23.5 70.5t-65.5 29.5z" /></g><g transform="matrix(.017,-0,0,-.017,62.907,12.162)"><path id="x3C" d="M512 -3l-437 233v51l437 233v-58l-378 -200v-2l378 -199v-58z" /></g><g transform="matrix(.017,-0,0,-.017,77.594,12.162)"><path id="x30" d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105&#xA;q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" /></g><g transform="matrix(.017,-0,0,-.017,85.753,12.162)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,89.629,12.162)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,97.788,12.162)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,105.948,12.162)"><use xlink:href="#x31"/></g><g transform="matrix(.017,-0,0,-.017,114.107,12.162)"><path id="x29" d="M275 270q0 -296 -211 -440l-19 23q75 62 116.5 174t41.5 243t-42 243t-116 173l19 24q211 -144 211 -440z" /></g>

		
	
</svg>. There were no significant differences between the patients with triglyceride levels &#x3e;150&#x2009;mg/dL <svg     style="vertical-align:-2.3205pt;width:78.637497px;" id="M4" height="15.0875" version="1.1" viewBox="0 0 78.637497 15.0875" width="78.637497"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,12.138)"><use xlink:href="#x28"/></g><g transform="matrix(.017,-0,0,-.017,5.944,12.138)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,21.464,12.138)"><path id="x3D" d="M535 323h-483v50h483v-50zM535 138h-483v50h483v-50z" /></g><g transform="matrix(.017,-0,0,-.017,36.168,12.138)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,44.327,12.138)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,48.203,12.138)"><path id="x36" d="M137 343l67 33q37 17 63 17q79 0 129.5 -53t50.5 -131q0 -92 -58 -156.5t-147 -64.5t-147 68t-58 182q0 63 17 119t43 95.5t61.5 72t69 52t67.5 31.5q62 22 128 33l6 -32q-56 -11 -108 -35q-149 -71 -184 -231zM227 337q-47 0 -95 -27q-6 -23 -6 -70q0 -93 36 -155.5&#xA;t96 -62.5q53 0 78 45.5t25 105.5q0 68 -35 116t-99 48z" /></g><g transform="matrix(.017,-0,0,-.017,56.362,12.138)"><use xlink:href="#x31"/></g><g transform="matrix(.017,-0,0,-.017,64.522,12.138)"><use xlink:href="#x38"/></g><g transform="matrix(.017,-0,0,-.017,72.681,12.138)"><use xlink:href="#x29"/></g>

		
	
</svg>. In conclusion, FF is a good method for estimating LDL-c in patients with metabolic syndrome.

Jos&#xe9; Knopfholz

Caio C&#xe9;sar Diniz Disserol

Andressa Jardim Pierin

Fernanda Let&#xed;cia Schirr

Larissa Streisky

Lilian Lumi Takito

Patr&#xed;cia Massucheto Ledesma

Jos&#xe9; Rocha Faria-Neto

Marcia Olandoski

Claudio Leinig Pereira da Cunha

Antonio Milton Bandeira

Validation of the Friedewald Formula in Patients with Metabolic Syndrome

Our current understanding of oxysterol metabolism during different disease states such as obesity and dyslipidemia is limited. Therefore, the aim of this study was to determine the effect of diet-induced obesity on the tissue distribution of various oxysterols and the mRNA expression of key enzymes involved in oxysterol metabolism. To induce obesity, male C57BL/6J mice were fed a high fat-cholesterol diet for 24 weeks. Following diet-induced obesity, plasma levels of 4<i  >&#x3B2;</i>-hydroxycholesterol, 5,6<i  >&#x3B1;</i>-epoxycholesterol, 5,6<i  >&#x3B2;</i>-epoxycholesterol, 7<i  >&#x3B1;</i>-hydroxycholesterol, 7<i  >&#x3B2;</i>-hydroxycholesterol, and 27-hydroxycholesterol were significantly (<svg     style="vertical-align:-0.1638pt;width:58.712502px;" id="M1" height="11.375" version="1.1" viewBox="0 0 58.712502 11.375" width="58.712502"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><path id="x1D443" d="M619 482q0 -69 -40.5 -119t-96 -72.5t-118.5 -26.5h-44l-70 20l-31 -151q-14 -67 0.5 -83t89.5 -22l-5 -28h-287l8 28q65 7 81.5 22t29.5 83l79 398q12 56 0.5 70.5t-78.5 20.5l7 28h255q108 0 164 -43t56 -125zM524 478q0 141 -146 141q-25 0 -47 -8q-16 -6 -20.5 -13.5&#xA;t-10.5 -39.5l-43 -241q37 -13 83 -13q67 0 125.5 45t58.5 129z" /></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><path id="x3C" d="M512 -3l-437 233v51l437 233v-58l-378 -200v-2l378 -199v-58z" /></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><path id="x30" d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105&#xA;q0 -76 10 -138.5t37 -107.5t69 -45q32 0 55.5 25t35.5 68.5t17.5 91.5t5.5 105t-5.5 105.5t-18 92t-36 68t-56.5 24.5z" /></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><path id="x2E" d="M113 -12q-24 0 -39.5 16t-15.5 42q0 24 16 40.5t40 16.5t40 -16.5t16 -40.5q0 -26 -16 -42t-41 -16z" /></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><path id="x35" d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8&#xA;l-26 -65h-233z" /></g>

		
	
</svg>) increased. In the liver and adipose tissue of the obese mice, 4<i  >&#x3B2;</i>-hydroxycholesterol was significantly (<svg     style="vertical-align:-0.1638pt;width:58.712502px;" id="M2" height="11.375" version="1.1" viewBox="0 0 58.712502 11.375" width="58.712502"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3C"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><use xlink:href="#x35"/></g>

		
	
</svg>) increased, whereas 27-hydroxycholesterol was increased only in the adipose tissue. No significant changes in either hepatic or adipose tissue mRNA expression were observed for oxysterol synthesizing enzymes 4<i  >&#x3B2;</i>-hydroxylase, 27-hydroxylase, or 7<i  >&#x3B1;</i>-hydroxylase. Hepatic mRNA expression of SULT2B1b, a key enzyme involved in oxysterol detoxification, was significantly (<svg     style="vertical-align:-0.1638pt;width:58.712502px;" id="M3" height="11.375" version="1.1" viewBox="0 0 58.712502 11.375" width="58.712502"  xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg">
	
		
			<g transform="matrix(.017,-0,0,-.017,.062,11.112)"><use xlink:href="#x1D443"/></g><g transform="matrix(.017,-0,0,-.017,15.582,11.112)"><use xlink:href="#x3C"/></g><g transform="matrix(.017,-0,0,-.017,30.286,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,38.446,11.112)"><use xlink:href="#x2E"/></g><g transform="matrix(.017,-0,0,-.017,42.321,11.112)"><use xlink:href="#x30"/></g><g transform="matrix(.017,-0,0,-.017,50.481,11.112)"><use xlink:href="#x35"/></g>

		
	
</svg>) elevated in the obese mice. Interestingly, the appearance of the large HDL<sub  >1</sub> lipoprotein was observed with increased oxysterol synthesis during obesity.  In diet-induced obese mice, dietary intake and endogenous enzymatic synthesis of oxysterols could not account for the increased oxysterol levels, suggesting that nonenzymatic cholesterol oxidation pathways may be responsible for the changes in oxysterol metabolism.

Joshua S. Wooten

Huaizhu Wu

Joe Raya

Xiaoyuan Dai Perrard

John Gaubatz

Ron C. Hoogeveen

The Influence of an Obesogenic Diet on Oxysterol Metabolism in C57BL/6J Mice

About this journal

Journal profile

Meet the editorial board

Editor spotlight

Submit your proposal

Do you think there is an emerging area of research that really needs to be highlighted? Or an existing research area that has been overlooked or would benefit from deeper investigation? Raise the profile of a research area by leading a Special Issue.

Cholesterol