Inhibition of the Ubiquitin-Activating Enzyme UBA1 Suppresses Diet-Induced Atherosclerosis in Apolipoprotein E-Knockout Mice

<div>Inhibition of UBA1 decreased proinflammatory cytokine levels in diet-induced atherosclerosis in <i>Apoe-/-</i> mice. (a) Flow cytometry analysis of circulating monocytes, neutrophils, and T cells. (b) Quantitative real-time PCR analysis of aortic expression of cytokines associated with monocyte recruitment (<i>Mcp-1</i>, <i>Vcam-1</i>, and <i>Icam-1</i>). (c) Quantitative real-time PCR analysis of aortic expression of macrophage-derived proinflammatory (<i>Il-1β</i>, <i>Il-6</i>, and <i>Tnfα</i>) and anti-inflammatory (<i>Il-4</i> and <i>Il-10</i>) cytokines. <svg height="8.55521pt" id="M9" style="vertical-align:-0.2063904pt" version="1.1" viewbox="-0.0498162 -8.34882 38.7456 8.55521" width="38.7456pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path 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"></path></g><g transform="matrix(.013,0,0,-0.013,10.158,0)"><path d="M535 323V373H52V323H535ZM535 138V188H52V138H535Z"></path></g><g transform="matrix(.013,0,0,-0.013,21.421,0)"><path 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"></path></g><g transform="matrix(.013,0,0,-0.013,27.661,0)"><path d="M300 253H71L57 198H286L300 253Z"></path></g><g transform="matrix(.013,0,0,-0.013,32.307,0)"><path 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"></path></g></svg> per group; <span class="nowrap"><svg height="6.01072pt" id="M10" style="vertical-align:-0.04980993pt" version="1.1" viewbox="-0.0498162 -5.96091 7.75925 6.01072" width="7.75925pt" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink"><g transform="matrix(.013,0,0,-0.013,0,0)"><path d="M471 153C471 170 463 194 452 212C400 220 373 229 322 255C373 281 400 290 452 298C463 316 471 339 471 357C456 366 431 371 410 370C377 329 356 310 308 279C311 336 317 364 336 413C326 432 310 451 294 459C279 451 262 432 252 413C271 364 277 336 280 279C232 310 211 329 178 370C157 371 132 367 117 357C117 340 125 316 136 298C188 290 215 281 266 255C215 229 188 220 136 212C125 194 117 171 117 153C132 144 157 139 178 140C211 181 232 200 280 231C277 174 271 146 252 97C262 78 278 59 294 51C309 59 326 78 336 97C317 146 311 174 308 231C356 200 377 181 410 140C431 139 456 143 471 153Z"></path></g></svg>:</span> &lt;0.05; ns: not significant.</div>

Journal of Immunology Research

fig4

Figure 4

Figure 4: Inhibition of the Ubiquitin-Activating Enzyme UBA1 Suppresses Diet-Induced Atherosclerosis in Apolipoprotein E-Knockout Mice 