<i>Objective</i>. We investigated the effects of resveratrol (Res) and MCC950 on the pyroptosis of vascular smooth muscle cells (VSMCs) and the potential pathway. <i>Methods and Results</i>. Compared with the control (Con) group, the atherosclerosis (AS) group showed calcified nodules, which suggested that the calcification medium induced the calcification of VSMCs. VSMCs showed proliferative activity and significantly attenuated calcification under treatment with 10 <i>μ</i>mol/L Res. The calcium salt was detected by alizarin red S staining. Res and MCC950 downregulated the calcification, inflammatory, pyroptosis, and transcription factor-related indicators all decreased by RT-qPCR with Western blot and immunofluorescence. The results showed that Res and MCC950 refrained the calcification of VSMCs and that Res has a better effect than MCC950. Plaques and calcium salt deposits were present in the carotid region in the control group. More calcium salt deposits were evident in the plaques of the Par group by HE staining and alizarin red S staining. The calcification indexes BMP2, Runx2, and related indexes declined by immunofluorescence, which showed parthenolide-inhibited AS. The related protein expressions were consistent with the expression of the cell experiments. <i>Conclusion</i>. Our data demonstrated that inflammatory response and pyroptosis exacerbate AS and unravel the link between VSMCs and the progression of AS lesions. Res and MCC950 inhibited the calcification of VSMCs by regulating NF-<i>κ</i>B/NLRP3/IL-1<i>β</i> signaling axis. P53 can exacerbate the AS lesions by acting on NLRP3 inflammasome and pyroptosis. Our findings supported the clinical applications of Res and MCC950 in VSMCs individuals to counteract pyroptosis and AS, and P53 inhibitors also can be a potential treatment for AS.

Shihuan Li

Qingjie Li

Qiaofeng Zhou

Suqin Li

Siqi Wang

Qing Yao

Changhan Ouyang

Chao Liu

Mincai Li

Attenuating Atherosclerosis through Inhibition of the NF-<i>κ</i>B/NLRP3/IL-1<i>β</i> Pathway-Mediated Pyroptosis in Vascular Smooth Muscle Cells (VSMCs)

Yao Yao

Yanli Li

Qinchun Jin

Xiaoye Li

Xiaochun Zhang

Qianzhou Lv

Perioperative Treatment with Rivaroxaban and Dabigatran on Changes of Coagulation and Platelet Activation Biomarkers following Left Atrial Appendage Closure

Endothelial-to-mesenchymal transition (EndMT) is the process by which endothelial cells lose their endothelial properties and acquire mesenchymal characteristics. Dual-specific protein phosphatase 22 (DUSP22) inactivates various protein kinases and transcription factors by dephosphorylating serine/threonine residues: hence, it plays a key role in many diseases. The aim of this study was to explore the functional role of DUSP22 in EndMT. In the transforming growth factor-<i>β</i>-induced EndMT model in human umbilical vein endothelial cells (HUVECs), we observed a downregulation of DUSP22 expression. This DUSP22 deficiency could aggravate EndMT. Conversely, the overexpression of DUSP22 could ameliorate EndMT. We used signaling pathway inhibitors to verify our results and found that DUSP22 could regulate EndMT through the smad2/3 and the mitogen-activated protein kinase (MAPK) signaling pathways. In summary, DUSP22 ameliorates EndMT in HUVECs in vitro through the smad2/3 and MAPK signaling pathways.

Lu Chen

Hongyu Su

Zekai Tao

Cui Liang

Zhongzhao Liu

Yiming Dong

Peipei Zheng

Yuan Liu

DUSP22 Ameliorates Endothelial-to-Mesenchymal Transition in HUVECs through Smad2/3 and MAPK Signaling Pathways

<i>Background</i>. Epidemiological studies conducted in extensive population cohorts have led to the creation of numerous cardiovascular risk predictor models. However, these tools have certain limitations that restrict its applicability. The aim behind the following work is to summarize today’s best-known limitations of cardiovascular risk assessment models through presenting the critical analyses conducted in this area, with the intention of offering practitioners a comprehensive understanding of these restrictions. Critical analyses revealed that these scales exhibit numerous limitations that could impact their performance. Most of these models evaluate cardiovascular risk based on classic risk factors and other restrictions, thereby negatively affecting their sensitivity. Scientists have made significant advancements in improving cardiovascular risk models, tailoring them to accommodate a wide range of populations and devising scales for estimating cardiovascular risks that can account for all prevailing restrictions. Better understanding these limitations could improve the cardiovascular risk stratification.

Ibtissam Talha

Noureddine Elkhoudri

Abderraouf Hilali

Major Limitations of Cardiovascular Risk Scores

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and hyperlipidemia is one major inducing factor of CVD. It is worthy to note that fucoidans are reported to have hypolipidemic activity with species specificity; however, the underlying mechanisms of action are far from clarification. This study is aimed at investigating the plasma lipid-lowering mechanisms of the fucoidan from <i>L. japonica</i> Aresch by detecting the levels of hepatic genes that are involved in lipid metabolism. Our results demonstrated that the fucoidan F3 significantly lowered total cholesterol and triglyceride in C57BL/6J mice fed a high-fat diet. In the mouse liver, fucoidan F3 intervention significantly increased the gene expression of peroxisome proliferator-activated receptor (PPAR) <i>α</i>, liver X receptor (LXR) <i>α</i> and <i>β</i>, and ATP-binding cassette transporter (ABC) G1 and G8 and decreased the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), low-density lipoprotein receptor, cholesterol 7 alpha-hydroxylase A1, and sterol regulatory element-binding protein (SREBP) 1c and SREBP-2. These results demonstrated that the antihyperlipidemic effects of fucoidan F3 are related to its activation of PPAR<i>α</i> and LXR/ABC signaling pathways and inactivation of SREBPs. In conclusion, fucoidan F3 may be explored as a potential compound for prevention or treatment of lipid disorders.

Yan Zhang

Tian Liu

Ze-Jie Qu

Xue Wang

Wen-Gang Song

Shou-Dong Guo

<i>Laminaria japonica</i> Aresch-Derived Fucoidan Ameliorates Hyperlipidemia by Upregulating LXRs and Suppressing SREBPs

<i>Background</i>. Quantitative flow ratio (QFR) is an angiography-based fractional flow reserve measurement without pressure wire or induction of hyperemia. A recent innovation that uses combined geometrical data and hemodynamic boundary conditions to measure QFR from a single angiographic view has shown the potential to measure QFR of the renal artery-renal QFR (rQFR). <i>Objective</i>. The aim of this pilot study was to assess the feasibility of rQFR measurement and the contribution of rQFR in selecting patients with atherosclerotic renal artery stenosis (ARAS) undergoing revascularization. <i>Methods</i>. This retrospective trial enrolled patients who had ARAS (50-90%) and hypertension. The enrolled patients were treated by optimal antihypertensive medication or revascularization, respectively, and the therapeutic strategies were based on rFFR measurement and/or clinical feature. <i>Results</i>. A total of 55 patients underwent rQFR measurement. Among the enrolled patients, 18 underwent optimal antihypertensive medication and 37 underwent revascularization, 19 patients in whom rQFR and rFFR were both assessed. During the 180-day follow-up, 25 patients saw an improvement in their blood pressure among the 37 patients that underwent revascularization. ROC analysis revealed that rQFR had a high diagnostic accuracy for predicting blood pressure improvement (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="58.918pt" style="vertical-align:-4.65666pt" id="M1" height="13.41pt" version="1.1" viewBox="-0.0498162 -8.75334 58.918 13.41"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g190-66" d="M673 0V28C608 34 594 43 563 129C499 303 432 494 370 665L339 656L132 132C98 43 84 37 20 28V0H238V28C162 35 154 45 175 108C188 150 203 192 219 237H432C454 176 474 122 487 83S491 36 428 28V0H673ZM418 280H234C265 362 296 450 328 535H330L418 280Z"/></g><g transform="matrix(.013,0,0,-0.013,8.226,0)"><path id="g190-86" d="M716 650H478V622C549 617 570 605 575 566C579 535 582 493 582 401V326C582 161 537 40 393 40C269 40 205 133 205 294V521C205 611 213 617 291 622V650H33V622C111 615 120 611 120 521V272C120 154 148 80 208 34C252 0 309 -14 368 -14C434 -14 501 7 548 55C605 116 623 201 623 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-160 712 -159L720 -138ZM348 25C231 49 146 172 146 342C146 533 249 629 360 629C497 629 601 510 601 302C601 142 523 51 443 28C434 34 425 41 416 47L348 25Z"/></g><g transform="matrix(.0091,0,0,-0.0091,36.614,3.132)"><path id="g190-71" d="M493 503C489 551 484 614 483 650H43V622C120 616 128 611 128 525V126C128 40 120 34 40 28V0H312V28C221 34 213 40 213 126V307H316C407 307 412 296 424 227H453V420H424C412 355 407 346 316 346H213V584C213 613 216 616 246 616H322C398 616 419 607 436 579C449 559 455 539 464 499L493 503Z"/></g><g transform="matrix(.0091,0,0,-0.0091,41.428,3.132)"><path id="g190-83" d="M631 18C609 24 585 35 559 65C534 91 514 117 478 169C448 214 406 281 389 313C462 346 516 399 516 485C516 545 490 590 449 616C412 641 363 650 290 650H42V622C120 615 128 612 128 527V125C128 40 120 34 38 28V0H300V28C221 34 212 40 212 125V284H244C295 284 312 272 329 244C359 195 395 133 430 84C475 19 516 -3 592 -7C603 -8 615 -8 627 -8L631 18ZM212 316V563C212 591 215 602 223 607C231 613 248 617 277 617C352 617 423 577 423 469C423 415 407 375 368 345C343 324 310 316 260 316H212Z"/></g><g transform="matrix(.013,0,0,-0.013,51.287,0)"><path id="g117-34" d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.157pt" style="vertical-align:-4.65666pt" height="13.41pt" version="1.1" viewBox="62.500183799999995 -8.75334 28.157 13.41"><g transform="matrix(.013,0,0,-0.013,62.55,0)"><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(.013,0,0,-0.013,68.79,0)"><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(.013,0,0,-0.013,71.754,0)"><path id="g113-58" d="M244 635C114 635 38 519 38 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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>,</span></span> 95% CI 0.798-0.998). The ideal cut-off value of rQFR for predicting blood pressure improvement after revascularization is ≤0.72 (sensitivity: 72.00%, specificity: 100%). The paired <svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" style="vertical-align:-0.2063999pt" id="M2" height="8.02022pt" version="1.1" viewBox="-0.0498162 -7.81382 4.54925 8.02022" width="4.54925pt"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-117" d="M324 430H196L233 583L223 592L145 529L120 430H54L29 396L31 388H111L56 126C33 15 54 -12 77 -12C137 -12 214 57 250 95L233 119C208 92 155 59 138 59C126 59 120 70 131 125L186 390L298 394L324 430Z"/></g></svg> test and Bland–Altman analyses demonstrated good agreement between rQFR and rFFR (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="15.696pt" style="vertical-align:-0.2063904pt" id="M3" height="8.55521pt" version="1.1" viewBox="-0.0498162 -8.34882 15.696 8.55521"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-117"/></g><g transform="matrix(.013,0,0,-0.013,8.065,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.173pt" style="vertical-align:-0.2063904pt" height="8.55521pt" version="1.1" viewBox="19.2781838 -8.34882 28.173 8.55521"><g transform="matrix(.013,0,0,-0.013,19.328,0)"><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(.013,0,0,-0.013,25.568,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,28.532,0)"><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(.013,0,0,-0.013,34.772,0)"><use xlink:href="#g113-57"/></g><g transform="matrix(.013,0,0,-0.013,41.012,0)"><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>,</span></span> 95% CI -0.021 to 0.001, 95% limits of agreement: -0.035 to 0.055, <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.973pt" style="vertical-align:-3.42938pt" id="M4" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.973 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><path id="g113-113" d="M570 304C570 398 525 448 414 448C385 448 343 445 312 434L329 511L321 518C297 504 262 482 244 460L233 411C195 397 159 381 128 358L135 332C160 347 189 360 224 373L111 -147C97 -210 84 -218 17 -231L13 -257L254 -247L259 -218L233 -216C183 -212 177 -202 189 -142L218 -1C238 -10 266 -12 283 -12C351 3 429 48 483 105C543 168 570 242 570 304ZM482 289C482 161 380 33 304 33C278 33 248 51 233 69L303 396C326 400 352 403 369 403C428 403 482 380 482 289Z"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.184pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 28.184 11.7782"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-56"/></g><g transform="matrix(.013,0,0,-0.013,44.291,0)"><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>).</span></span> The Spearman correlation test reveals that there was a significant positive correlation between rQFR and rFFR (<span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="16.751pt" style="vertical-align:-0.2063904pt" id="M5" height="8.55521pt" version="1.1" viewBox="-0.0498162 -8.34882 16.751 8.55521"><g transform="matrix(.013,0,0,-0.013,0,0)"><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(.013,0,0,-0.013,9.12,0)"><use xlink:href="#g117-34"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.175pt" style="vertical-align:-0.2063904pt" height="8.55521pt" version="1.1" viewBox="20.3331838 -8.34882 28.175 8.55521"><g transform="matrix(.013,0,0,-0.013,20.383,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,26.623,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,29.587,0)"><use xlink:href="#g113-58"/></g><g transform="matrix(.013,0,0,-0.013,35.828,0)"><use xlink:href="#g113-54"/></g><g transform="matrix(.013,0,0,-0.013,42.068,0)"><use xlink:href="#g113-51"/></g></svg>,</span></span> 95% CI 0.874 to 0.982, <span class="inline_break"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="18.973pt" style="vertical-align:-3.42938pt" id="M6" height="11.7782pt" version="1.1" viewBox="-0.0498162 -8.34882 18.973 11.7782"><g transform="matrix(.013,0,0,-0.013,0,0)"><use xlink:href="#g113-113"/></g><g transform="matrix(.013,0,0,-0.013,11.342,0)"><path id="g117-91" d="M512 -3V55L134 254V256L512 456V514L75 281V230L512 -3Z"/></g></svg><span class="irelop"/><span class="nowrap"><svg xmlns:xlink="http://www.w3.org/1999/xlink" xmlns="http://www.w3.org/2000/svg" width="28.184pt" style="vertical-align:-3.42938pt" height="11.7782pt" version="1.1" viewBox="22.555183800000002 -8.34882 28.184 11.7782"><g transform="matrix(.013,0,0,-0.013,22.605,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,28.845,0)"><use xlink:href="#g113-47"/></g><g transform="matrix(.013,0,0,-0.013,31.809,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,38.049,0)"><use xlink:href="#g113-49"/></g><g transform="matrix(.013,0,0,-0.013,44.289,0)"><use xlink:href="#g113-50"/></g></svg>).</span></span> <i>Conclusion</i>. The rQFR has the potential to enhance the ability of angiography to detect functionally significant renal artery stenosis during angiography and to produce results that are comparable to invasive hemodynamic assessment.

Xiang Huang

Xiao-Lan Li

Heng Zhou

Xiao-Mei Li

Assessment of Angiography-Based Renal Quantitative Flow Ratio Measurement in Patients with Atherosclerotic Renal Artery Stenosis

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<p><em>Cardiovascular Therapeutics</em> publishes original research and review articles focusing on cardiovascular and clinical pharmacology, as well as clinical trials of novel cardiovascular therapies.</p>


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Cardiovascular Therapeutics - Table of contents 2024

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Cardiovascular Therapeutics publishes original research and review articles focusing on cardiovascular and clinical pharmacology, as well as clinical trials of novel cardiovascular therapies.

Cardiovascular Therapeutics