{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T23:15:39Z","timestamp":1794438939998,"version":"4.9.1"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"2","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 HL156849"],"award-info":[{"award-number":["R01 HL156849"]}]},{"name":"NIH","award":["R01 HL136314"],"award-info":[{"award-number":["R01 HL136314"]}]},{"name":"NIH","award":["R01 HL141425"],"award-info":[{"award-number":["R01 HL141425"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,23]]},"abstract":"<jats:p>\n                    The use of senolytic agents to remove senescent cells from atherosclerotic lesions is controversial. A common limitation of previous studies is the failure to rigorously define the effects of senolytic agent ABT-263 (Navitoclax) on smooth muscle cells (SMC) despite studies claiming that these cells are the major source of senescent cells. Moreover, there are no studies on the effect of ABT-263 on endothelial cells (EC), which \u2014 along with SMC \u2014 comprise 90% of \u03b1-smooth muscle actin\n                    <jats:sup>+<\/jats:sup>\n                    (\u03b1-SMA\n                    <jats:sup>+<\/jats:sup>\n                    ) myofibroblast-like cells in the protective fibrous cap. Here we tested the hypothesis that treatment of advanced atherosclerotic mice with ABT-263 will reduce lesion size and increase plaque stability. SMC (Myh11-CreER\n                    <jats:sup>T2<\/jats:sup>\n                    -eYFP) and EC (Cdh5-CreER\n                    <jats:sup>T2<\/jats:sup>\n                    -eYFP) lineage tracing\n                    <jats:italic>\n                      Apoe\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice were fed a western diet (WD) for 18 weeks, followed by ABT-263 at 100 mg\/kg\/bw for 6 weeks or 50 mg\/kg\/bw for 9 weeks. ABT-263 treatment did not change lesion size or lumen area of the brachiocephalic artery (BCA). However, ABT-263 treatment reduced SMC by 90% and increased EC contributions to lesions via EC-to-mesenchymal transition (EndoMT) by 60%. ABT-263 treatment also reduced \u03b1-SMA\n                    <jats:sup>+<\/jats:sup>\n                    fibrous cap thickness by 60% and was associated with a &gt; 50% mortality rate. Taken together, ABT-263 treatment of WD-fed\n                    <jats:italic>\n                      Apoe\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice with advanced lesions resulted in multiple detrimental changes, including reduced indices of stability and increased mortality.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.173863","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T14:00:38Z","timestamp":1705932038000},"source":"Crossref","is-referenced-by-count":35,"title":["Treatment of advanced atherosclerotic mice with ABT-263 reduced indices of plaque stability and increased 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