{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:24:10Z","timestamp":1788449050589,"version":"build-2803163510"},"reference-count":61,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"18","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,9,21]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Aldehyde dehydrogenase\u20102 (ALDH2), a mitochondrial enzyme, detoxifies reactive aldehydes such as 4\u2010hydroxy\u20102\u2010nonenal (4HNE). A highly prevalent E487K mutation in ALDH2 (ALDH2*2) in East Asian people with intrinsic low ALDH2 activity is implicated in diabetic complications. 4HNE\u2010induced cardiomyocyte dysfunction was studied in diabetic cardiac damage; however, coronary endothelial cell (CEC) injury in myocardial ischemia\u2010reperfusion injury (IRI) in diabetic mice has not been studied. Therefore, we hypothesize that the lack of ALDH2 activity exacerbates 4HNE\u2010induced CEC dysfunction which leads to cardiac damage in ALDH2*2 mutant diabetic mice subjected to myocardial IRI.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Three weeks after diabetes mellitus (DM) induction, hearts were subjected to IRI either in vivo via left anterior descending artery occlusion and release or ex vivo IRI by using the Langendorff system. The cardiac performance was assessed by conscious echocardiography in mice or by inserting a balloon catheter in the left ventricle in the ex vivo model. Just 3\u00a0weeks of DM led to an increase in cardiac 4HNE protein adducts and, cardiac dysfunction, and a decrease in the number of CECs along with reduced myocardial ALDH2 activity in ALDH2*2 mutant diabetic mice compared with their wild\u2010type counterparts. Systemic pretreatment with Alda\u20101 (10\u00a0mg\/kg per day), an activator of both ALDH2 and ALDH2*2, led to a reduction in myocardial infarct size and dysfunction, and coronary perfusion pressure upon cardiac IRI by increasing CEC population and coronary arteriole opening.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Low ALDH2 activity exacerbates 4HNE\u2010mediated CEC injury and thereby cardiac dysfunction in diabetic mouse hearts subjected to IRI, which can be reversed by ALDH2 activation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.021140","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T08:56:36Z","timestamp":1630918596000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Diabetic Aldehyde Dehydrogenase 2 Mutant (ALDH2*2) Mice Are More Susceptible to Cardiac Ischemic\u2010Reperfusion Injury Due to 4\u2010Hydroxy\u20102\u2010Nonenal Induced Coronary Endothelial Cell Damage"],"prefix":"10.1161","volume":"10","author":[{"given":"Guodong","family":"Pan","sequence":"first","affiliation":[{"name":"Division of Hypertension and Vascular Research Department of Internal Medicine Henry Ford Health System Detroit MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6472-951X","authenticated-orcid":false,"given":"Bipradas","family":"Roy","sequence":"additional","affiliation":[{"name":"Division of Hypertension and Vascular Research Department of Internal Medicine Henry Ford Health System Detroit MI"},{"name":"Department of Physiology Wayne State University Detroit MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7559-8041","authenticated-orcid":false,"given":"Suresh 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