{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:24:38Z","timestamp":1792077878709,"version":"4.4.0"},"reference-count":75,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2024,8,2]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>PANX1 (pannexin 1), a ubiquitously expressed ATP release membrane channel, has been shown to play a role in inflammation, blood pressure regulation, and myocardial infarction. However, the possible role of PANX1 in cardiomyocytes in the progression of heart failure has not yet been investigated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHOD:<\/jats:title>\n            <jats:p>\n              We generated a novel mouse line with constitutive deletion of PANX1 in cardiomyocytes (Panx1\n              <jats:sup>MyHC6<\/jats:sup>\n              ).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              PANX1 deletion in cardiomyocytes had no effect on unstressed heart function but increased the glycolytic metabolism and resulting glycolytic ATP production, with a concurrent decrease in oxidative phosphorylation, both in vivo and in vitro. In vitro, treatment of H9c2 (H9c2 rat myoblast cell line) cardiomyocytes with isoproterenol led to PANX1-dependent release of ATP and Yo-Pro-1 uptake, as assessed by pharmacological blockade with spironolactone and siRNA-mediated knockdown of PANX1. To investigate nonischemic heart failure and the preceding cardiac hypertrophy, we administered isoproterenol, and we demonstrated that Panx1\n              <jats:sup>MyHC6<\/jats:sup>\n              mice were protected from systolic and diastolic left ventricle volume increases as a result of cardiomyocyte hypertrophy. Moreover, we found that Panx1\n              <jats:sup>MyHC6<\/jats:sup>\n              mice showed decreased isoproterenol-induced recruitment of immune cells (CD45\n              <jats:sup>+<\/jats:sup>\n              ), particularly neutrophils (CD11b\n              <jats:sup>+<\/jats:sup>\n              [integrin subunit alpha M], Ly6g\n              <jats:sup>+<\/jats:sup>\n              [lymphocyte antigen 6 family member G]), to the myocardium.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Together, these data demonstrate that PANX1 deficiency in cardiomyocytes increases glycolytic metabolism and protects against cardiac hypertrophy in nonischemic heart failure at least in part by reducing immune cell recruitment. Our study implies PANX1 channel inhibition as a therapeutic approach to ameliorate cardiac dysfunction in patients with heart failure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.124.324650","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T09:01:21Z","timestamp":1719997281000},"page":"503-517","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Cardiomyocyte PANX1 Controls Glycolysis and Neutrophil Recruitment in Hypertrophy"],"prefix":"10.1161","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7470-7285","authenticated-orcid":true,"given":"Caitlin M.","family":"Pavelec","sequence":"first","affiliation":[{"name":"Department of Pharmacology (C.M.P., H.L.L., E.E.O., A.S., S.H.T., S.Y., C.M.U., N.L.), University of Virginia School of Medicine, Charlottesville."},{"name":"Robert M. Berne Cardiovascular Research Center (C.M.P., A.P.Y., B.E.I., M.J.W., N.L.), University of Virginia School of Medicine, Charlottesville."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander P.","family":"Young","sequence":"additional","affiliation":[{"name":"Cardiovascular Medicine, Department of Medicine (A.P.Y., M.J.W.), University of Virginia School of Medicine, Charlottesville."},{"name":"Robert M. 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