{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:19:09Z","timestamp":1777497549385,"version":"3.51.4"},"reference-count":44,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CH"],"published-print":{"date-parts":[[2024,6,25]]},"abstract":"<jats:p>BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) were reported to protect from hypoxia-induced oxidative stress in coronary endothelial cells (CECs) after acute myocardial infarction (AMI). Nrf2 shows a protective effect in hypoxia-induced CECs after AMI. Plasmalemma vesicle-associated protein (PLVAP) plays a pivotal role in angiogenesis after AMI. AIM: To explore the protective effect of ACEIs and the involved mechanisms under hypoxia challenge. METHODS: Human coronary endothelial cells (HCAECs) were used to establish hypoxia-induced oxidative stress injury in vitro. Flow cytometry was used to evaluate the protective effect of ACEI on hypoxia conditions.ET-1, NO, ROS, and VEGF were detected by ELISA. HO-1, Nrf2, and Keap-1, the pivotal member in the Nrf2 signaling pathway, eNOS and PLVAP were detected in HEAECs treated with ACEI by immunofluorescence, qPCR, and western blotting. RESULTS: The hypoxia ACEI or Nrf2 agonist groups showed higher cell viability compared with the hypoxia control group at 24 (61.75\u00b11.16 or 61.23\u00b10.59 vs. 44.24\u00b10.58, both P\u200a&lt;\u200a0.05) and 48\u200ah (41.85\u00b11.19 or 59.64\u00b11.13 vs. 22.98\u00b10.25, both P\u200a&lt;\u200a0.05). ACEI decreased the levels of ET-1 and ROS under hypoxia challenge at 24 and 48\u200ah (all P\u200a&lt;\u200a0.05); ACEI increased the VEGF and NO levels (all P\u200a&lt;\u200a0.05). ACEI promoted the expression level of eNOS, HO-1, Nrf2 and PLVAP but inhibited Keap-1 expression at the mRNA and protein levels (all P\u200a&lt;\u200a0.05). Blockade of the Nrf2 signaling pathway significantly decreased the expression level of PLVAP. CONCLUSION: ACEI protects hypoxia-treated HEAECs by activating the Nrf2 signaling pathway and upregulating the expression of PLVAP.<\/jats:p>","DOI":"10.3233\/ch-232007","type":"journal-article","created":{"date-parts":[[2024,2,9]],"date-time":"2024-02-09T10:33:51Z","timestamp":1707474831000},"page":"141-170","source":"Crossref","is-referenced-by-count":2,"title":["Angiotensin-converting enzyme inhibitors provide a protective effect on hypoxia-induced injury in human coronary artery endothelial cells via Nrf2 signaling and PLVAP"],"prefix":"10.1177","volume":"87","author":[{"given":"Qiubing","family":"Zhang","sequence":"first","affiliation":[{"name":"Tianjin Medical University, Tianjin, China"},{"name":"Department of Cardiology, Guang Yuan Central Hospital, Guang Yuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Gou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guang Yuan Central Hospital, Guang Yuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guang Yuan Central Hospital, Guang Yuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guang Yuan Central Hospital, Guang Yuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhitao","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guang Yuan Central Hospital, Guang Yuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingfang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guang Yuan Central Hospital, Guang Yuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guang Yuan Central Hospital, Guang Yuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanjun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guang Yuan Central Hospital, Guang Yuan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Cangzhou Central Hospital, Tianjin Medical University, Cangzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","reference":[{"key":"10.3233\/CH-232007_ref1","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1136\/heartjnl-2013-304721","article-title":"Socioeconomic inequalities in acute myocardial infarction incidence in migrant groups: has the epidemic arrived? analysis of nation-wide 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