{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:59:11Z","timestamp":1793642351030,"version":"4.5.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771315"],"award-info":[{"award-number":["81771315"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Diabetes-aggravated myocardial ischemia\u2013reperfusion (MI\/R) injury remains an urgent medical issue, and the molecular mechanisms involved with diabetes and MI\/R injury remain largely unknown. Previous studies have shown that inflammation and P2X7 signaling participate in the pathogenesis of the heart under individual conditions. It remains to be explored if P2X7 signaling is exacerbated or alleviated under double insults. We established a high-fat diet and streptozotocin-induced diabetic mouse model, and we compared the differences in immune cell infiltration and P2X7 expression between diabetic and nondiabetic mice after 24 h of reperfusion. The antagonist and agonist of P2X7 were administered before and after MI\/R. Our study showed that the MI\/R injury of diabetic mice was characterized by increased infarct area, impaired ventricular contractility, more apoptosis, aggravated immune cell infiltration, and overactive P2X7 signaling compared with nondiabetic mice. The major trigger of increased P2X7 was the MI\/R-induced recruitment of monocytes and macrophages, and diabetes can be a synergistic factor in this process. Administration of P2X7 agonist eliminated the differences in MI\/R injury between nondiabetic mice and diabetic mice. Both 2 wk of brilliant blue G injection before MI\/R and acutely administered A438079 at the time of MI\/R injury attenuated the role of diabetes in exacerbating MI\/R injury, as evidenced by decreased infarct size, improved cardiac function, and inhibition of apoptosis. Additionally, brilliant blue G blockade decreased the heart rate after MI\/R, which was accompanied by downregulation of tyrosine hydroxylase expression and nerve growth factor transcription. In conclusion, targeting P2X7 may be a promising strategy for reducing the risk of MI\/R injury in diabetes.<\/jats:p>","DOI":"10.4049\/jimmunol.2200838","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T12:23:29Z","timestamp":1683289409000},"page":"1962-1973","source":"Crossref","is-referenced-by-count":8,"title":["Upregulation of P2X7 Exacerbates Myocardial Ischemia\u2013Reperfusion Injury through Enhancing Inflammation and Apoptosis in Diabetic Mice"],"prefix":"10.1093","volume":"210","author":[{"given":"Fancan","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Zhujiang Hospital, Southern Medical University , Guangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Zhujiang Hospital, Southern Medical University , Guangzhou,","place":["China"]},{"name":"Department of Anesthesiology, Huazhong University of Science and Technology Union Shenzhen Hospital , Shenzhen,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxin","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Zhujiang Hospital, Southern Medical University , Guangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Zhujiang Hospital, Southern Medical University , Guangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2613-0036","authenticated-orcid":false,"given":"Shiyuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Zhujiang Hospital, Southern Medical University , Guangzhou,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,5]]},"reference":[{"key":"2025021008072234700_r1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/nrendo.2015.10","article-title":"Adenosine signalling in diabetes mellitus--pathophysiology and therapeutic considerations","volume":"11","author":"Antonioli","year":"2015","journal-title":"Nat. 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