{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T18:52:49Z","timestamp":1778611969063,"version":"3.51.4"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,4,18]],"date-time":"2020-04-18T00:00:00Z","timestamp":1587168000000},"content-version":"vor","delay-in-days":108,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470577"],"award-info":[{"award-number":["81470577"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p><jats:italic>Objective<\/jats:italic>. The P2Y<jats:sub>6<\/jats:sub> receptor has been shown to be involved in many cardiovascular diseases, including hypertension and atherosclerosis. The study is aimed at exploring the role of the P2Y<jats:sub>6<\/jats:sub> receptor in Ang II\u2010induced abdominal aortic aneurysm (AAA) formation in apolipoprotein E\u2010deficient (apoE<jats:sup>-\/-<\/jats:sup>) mice by using its selective antagonist. <jats:italic>Methods<\/jats:italic>. Male apoE<jats:sup>-\/-<\/jats:sup> mice were fed with high\u2010fat diet and infused with angiotensin (Ang) II (1000\u2009ng\/kg\/min) for 4 weeks to induce AAA or saline as controls. Mice were divided into four groups: normal saline (NS, placebo control) group (<jats:italic>n<\/jats:italic> = 8), Ang II+vehicle (Ang II) group (<jats:italic>n<\/jats:italic> = 14), Ang II\u2010low dose MRS2578 (Ang II+MRS\u201016\u2009mg) group (<jats:italic>n<\/jats:italic> = 14), and Ang II\u2010high dose MRS2578 (Ang II+MRS\u201032\u2009mg) group (<jats:italic>n<\/jats:italic> = 14). Daily intraperitoneal injection with vehicle or MRS2578 was pretreated one week before Ang II infusion. On postoperative day 10, aorta imaging of each group was taken by ultrasonography. After 4 weeks of Ang II infusion, the excised aortas were processed for diameter measurement and quantification of aneurysm severity and tissue characteristics; the blood samples were collected for measurement of the lipid profile and levels of cytokines. Verhoeff\u2019s Van Gieson (EVG) staining and immunochemistry staining were performed to evaluate disruption of the extracellular matrix (ECM) and infiltration of macrophages. Expression and activity of matrix metalloproteinases (MMPs) was measured by gelatin zymography. <jats:italic>Results<\/jats:italic>. Treatment with MRS2578 made no significant difference in AAA formation, and maximal aortic diameter yet caused higher AAA rupture\u2010induced mortality from 7% (Ang II) to 21.4% (Ang II+MRS\u201016\u2009mg) or 42.9% (Ang II+MRS\u201032\u2009mg), respectively (<jats:italic>p<\/jats:italic> &lt; 0.05). Consistently, the severity of aneurysm tended to be more deteriorated in MRS2578\u2010treated groups, especially the high\u2010dosage group. The ratios of type III and IV aneurysm were much higher in the MRS2578\u2010coadministered groups (<jats:italic>p<\/jats:italic> &lt; 0.05). Furthermore, histological analyses showed that administration of MRS2578 significantly increased infiltration of macrophages, expression of monocyte chemotactic protein 1 (MCP\u20101) and vascular cell adhesion molecule\u20101 (VCAM\u20101), and activities of MMP\u20102 and MMP\u20109 followed by aggravating degradation elastin in vivo (<jats:italic>p<\/jats:italic> &lt; 0.05). However, the multiple effects of MRS2578 on the development of AAA are independent of changes in systolic blood pressure and lipid profiles. <jats:italic>Conclusions<\/jats:italic>. The present study demonstrated that administration of MRS2578 exacerbated the progression and rupture of experimental AAA through promoting proinflammatory response and MMP expression and activity, which indicated a crucial role of the P2Y<jats:sub>6<\/jats:sub> receptor in AAA development. <jats:italic>Clinical Relevance<\/jats:italic>. Purinergic P2Y receptors have attracted much attention since the P2Y<jats:sub>12<\/jats:sub> receptor antagonist had been successfully applied in clinical practice. Elucidating the underlying mechanisms of AAA and exploring potential therapeutic strategies are essential to prevent its progression and reduce the mortality rate.<\/jats:p>","DOI":"10.1155\/2020\/1983940","type":"journal-article","created":{"date-parts":[[2020,4,18]],"date-time":"2020-04-18T23:30:17Z","timestamp":1587252617000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Role of a Selective P2Y<sub>6<\/sub> Receptor Antagonist, MRS2578, on the Formation of Angiotensin II\u2010Induced Abdominal Aortic 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