{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T17:57:19Z","timestamp":1764784639735,"version":"3.41.2"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T00:00:00Z","timestamp":1618358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> To observe the effect of Si-Miao-Yong-An (SMYA) on atherosclerosis (AS) vulnerable plaques, and to further explore the mechanism by vasa vasorum (VV) angiogenesis and maturation as an entry point.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> SPF-class healthy male ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice were randomized into model group, simvastatin group and SMYA group, and C57BL\/6 mice were used as the control group. After 8 weeks of intervention, the pathological morphology of plaque was observed by HE staining; the VV density in plaque and aortic adventitia were observed by immunohistochemistry; VV maturation was measured by double-labelling immunofluorescence; the critical proteins of HIF-1\u03b1-Apelin\/APJ and Ang-1\/Tie signal pathways were detected by western blotting.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> SMYA decreased the plaque area and the ratio of plaque to lumen area; increased the minimum thickness of fibrous cap and its effect was greater than simvastatin. SMYA suppressed the VV neovascularization; promoted smooth muscle cells recruitment and VV maturation, which maintained plaque stability; its effect was obviously superior to simvastatin. SMYA deceased the expression of HIF-1\u03b1, Apelin, APJ, Phospho-MEK1\/2 (Ser217\/221), Phospho-p44\/42 MAPK (Erk1\/2) (Thr202\/Tyr204), Phospho-p70 S6 Kinase (Thr421\/Ser424), Ang-2 and Tie-2; it also increased the expression of Ang-1, Phospho-Akt (Ser473), Phospho-FOXO1 (Ser256) and Survivin.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> SMYA can decrease the AS plaque area in ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> mice, suppress the VV neovascularization and promote the VV maturation, and stabilize AS vulnerable plaque. The mechanism could be regulating the HIF-1\u03b1-Apelin\/APJ and Ang-1\/Tie signal pathways.<\/jats:p>","DOI":"10.3389\/fphar.2021.634611","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T05:57:20Z","timestamp":1618552640000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Effect and Mechanism of Si-Miao-Yong-An on Vasa Vasorum Remodeling in ApoE\u2212\/\u2212 Mice with Atherosclerosis Vulnerable Plague"],"prefix":"10.3389","volume":"12","author":[{"given":"Meng","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongwen","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueyao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,14]]},"reference":[{"key":"B26","doi-asserted-by":"publisher","first-page":"471","DOI":"10.3390\/cells8050471","article-title":"Role of angiopoietin-2 in vascular physiology and pathophysiology","volume":"8","author":"Akwii","year":"2019","journal-title":"Cells"},{"key":"B5","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1056\/NEJM198401193100307","article-title":"Hypothesis: vasa vasorum and neovascularization of human coronary arteries. 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