title: HSPA12B Attenuated Acute Myocardial Ischemia/reperfusion Injury via Maintaining Endothelial Integrity in a PI3K/Akt/mTOR-dependent Mechanism.
abstract: Endothelial damage is a critical mediator of myocardial ischemia/reperfusion (I/R) injury. HSPA12B is an endothelial-cell-specifically expressed heat shock protein. However, the roles of HSPA12B in acute myocardial I/R injury is unknown. Here we reported that myocardial I/R upregulated HSPA12B expression in ventricular tissues, and endothelial overexpression of HSPA12B in transgenic mice (Tg) limited infarct size, attenuated cardiac dysfunction and improved cardiomyocyte survival compared with their wild type littermates. These improvements were accompanied with the diminished myocardial no-reflow phenomenon, decreased microvascular leakage, and better maintained endothelial tight junctions. The I/R-evoked neutrophil infiltration was also suppressed in Tg hearts compared with its wild type (WT) littermates. Moreover, Tg hearts exhibited the enhanced activation of PI3K/Akt//mTOR signaling following I/R challenge. However, pharmacological inhibition of PI3K abolished the HSPA12B-induced cardioprotection against myocardial I/R injury. The data demonstrate for the first time that the endothelial HSPA12B protected hearts against myocardial I/R injury. This cardioprotective action of HSPA12B was mediated, at least in part, by improving endothelial integrity in a PI3K/Akt/mTOR-dependent mechanism. Our study suggests that targeting endothelial HSPA12B could be an alternative approach for the management of patients with myocardial I/R injury.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Kong
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Leyang
authors.initials: L
authors.lastname: Dai
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yana
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Departments of Surgery, East Tennessee State University, Johnson City, TN37614, USA.
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Surong
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Pathophysiology, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Zhengnian
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D004727:Endothelium / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D020556:Neutrophil Infiltration; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D018754:Ventricular Dysfunction
chemical_list: D018840:HSP70 Heat-Shock Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D019010:Vascular Cell Adhesion Molecule-1; C472131:HSPA12B protein, human