{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:08:01Z","timestamp":1792858081856,"version":"4.5.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2020,3,24]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Diabetes mellitus exacerbates myocardial ischemia\/reperfusion (MI\/R) injury by incompletely understood mechanisms. Adipocyte dysfunction contributes to remote organ injury. However, the molecular mechanisms linking dysfunctional adipocytes to increased MI\/R injury remain unidentified. The current study attempted to clarify whether and how small extracellular vesicles (sEV) may mediate pathological communication between diabetic adipocytes and cardiomyocytes, exacerbating MI\/R injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Adult male mice were fed a normal or a high-fat diet for 12 weeks. sEV (from diabetic serum, diabetic adipocytes, or high glucose\/high lipid-challenged nondiabetic adipocytes) were injected intramyocardially distal of coronary ligation. Animals were subjected to MI\/R 48 hours after injection.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>Intramyocardial injection of diabetic serum sEV in the nondiabetic heart significantly exacerbated MI\/R injury, as evidenced by poorer cardiac function recovery, larger infarct size, and greater cardiomyocyte apoptosis. Similarly, intramyocardial or systemic administration of diabetic adipocyte sEV or high glucose\/high lipid-challenged nondiabetic adipocyte sEV significantly exacerbated MI\/R injury. Diabetic epididymal fat transplantation significantly increased MI\/R injury in nondiabetic mice, whereas administration of a sEV biogenesis inhibitor significantly mitigated MI\/R injury in diabetic mice. A mechanistic investigation identified that miR-130b-3p is a common molecule significantly increased in diabetic serum sEV, diabetic adipocyte sEV, and high glucose\/high lipid-challenged nondiabetic adipocyte sEV. Mature (but not primary) miR-130b-3p was significantly increased in the diabetic and nondiabetic heart subjected to diabetic sEV injection. Whereas intramyocardial injection of a miR-130b-3p mimic significantly exacerbated MI\/R injury in nondiabetic mice, miR-130b-3p inhibitors significantly attenuated MI\/R injury in diabetic mice. Molecular studies identified AMPK\u03b11\/\u03b12, Birc6, and Ucp3 as direct downstream targets of miR-130b-3p. Overexpression of these molecules (particularly AMPK\u03b12) reversed miR-130b-3p induced proapoptotic\/cardiac harmful effect. Finally, miR-130b-3p levels were significantly increased in plasma sEV from patients with type 2 diabetes mellitus. Incubation of cardiomyocytes with diabetic patient sEV significantly exacerbated ischemic injury, an effect blocked by miR-130b-3p inhibitor.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>We demonstrate for the first time that miR-130b-3p enrichment in dysfunctional adipocyte-derived sEV, and its suppression of multiple antiapoptotic\/cardioprotective molecules in cardiomyocytes, is a novel mechanism exacerbating MI\/R injury in the diabetic heart. Targeting miR-130b-3p mediated pathological communication between dysfunctional adipocytes and cardiomyocytes may be a novel strategy attenuating diabetic exacerbation of MI\/R injury.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.119.042640","type":"journal-article","created":{"date-parts":[[2020,1,10]],"date-time":"2020-01-10T10:00:14Z","timestamp":1578650414000},"page":"968-983","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":179,"title":["Small Extracellular Microvesicles Mediated Pathological Communications Between Dysfunctional Adipocytes and Cardiomyocytes as a Novel Mechanism Exacerbating Ischemia\/Reperfusion Injury in Diabetic Mice"],"prefix":"10.1161","volume":"141","author":[{"given":"Lu","family":"Gan","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine and Medicine, Thomas Jefferson University, Philadelphia, PA (L.G., D.X., J.L, W.B.L., T.A.C., B.L., L.Z., X.-L.M., Y.W.)."},{"name":"Laboratory of Anesthesia and Critical Care Medicine, Department of Anesthesiology, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China (L.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine and Medicine, Thomas Jefferson University, Philadelphia, PA (L.G., D.X., J.L, W.B.L., T.A.C., B.L., L.Z., X.-L.M., Y.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine and Medicine, Thomas Jefferson University, Philadelphia, PA (L.G., D.X., J.L, W.B.L., T.A.C., B.L., L.Z., X.-L.M., Y.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne","family":"Bond Lau","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine and Medicine, Thomas Jefferson University, Philadelphia, PA (L.G., D.X., J.L, W.B.L., T.A.C., B.L., L.Z., X.-L.M., Y.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore A.","family":"Christopher","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine and Medicine, Thomas Jefferson University, Philadelphia, PA (L.G., D.X., J.L, W.B.L., T.A.C., B.L., L.Z., X.-L.M., Y.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Lopez","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine and Medicine, Thomas Jefferson University, Philadelphia, PA (L.G., D.X., J.L, W.B.L., T.A.C., B.L., L.Z., X.-L.M., Y.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine and Medicine, Thomas Jefferson University, Philadelphia, PA (L.G., D.X., J.L, W.B.L., T.A.C., B.L., L.Z., X.-L.M., Y.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhe","family":"Gao","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Temple University, Philadelphia, PA (E.G., W.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Koch","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Temple University, Philadelphia, PA (E.G., W.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Liang","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine and Medicine, Thomas Jefferson University, Philadelphia, PA (L.G., D.X., J.L, W.B.L., T.A.C., B.L., L.Z., X.-L.M., Y.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine and Medicine, Thomas Jefferson University, Philadelphia, PA (L.G., D.X., J.L, W.B.L., 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