title: Over-expression of HSPA12B protects mice against myocardium ischemic/reperfusion injury through a PPARγ-dependent PI3K/Akt/eNOS pathway.
abstract: Acute myocardial ischemia/reperfusion (MIR) injury leads to severe arrhythmias and a high lethality. We aim to determine the effect of heat shock protein A12B (HSPA12B), a newly discovered member of the Hsp70 family, on heart injury parameters following MIR surgery. We used HSPA12B transgenic mice to determine its effects on heart function parameters, infarct size and cellular apoptosis following MIR surgery. Proinflammatory cytokines, oxidative products and anti-oxidative enzymes in the myocardium were measured to evaluate the anti-inflammatory and anti-oxidative effects of HSPA12B over-expression. The role of PPARs/eNOS/PI3k/Akt pathway was investigated using their inhibitors. The alteration of hemodynamic parameters, histopathological, apoptotic and infarct size caused by MIR was greatly attenuated in HSPA12B over-expressed mice. HSPA12B also greatly mitigated the inflammatory response, demonstrated by the decrease in the levels of IL-1β, IL-6, TNF-a and MPO. Anti-oxidative enzymes (SOD, Catalase and GPx) were restored by HSPA12B; oxidative products (8-OHdG, MDA and protein carbonyl) were decreased. HSPA12B activated the PPARγ-dependent eNOS/PI3k/Akt pathway, and the influence of HSPA12B on cardiac function was reversed by the inhibitors of eNOS, PPARγ, Akt and PI3K. Our results present a novel signaling mechanism that HSPA12B protects MIR injury through a PPARγ-dependent PI3K/Akt/eNOS pathway.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine Shanghai, China.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine Shanghai, China.
authors.forename: Lincai
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine Shanghai, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine Shanghai, China.
authors.forename: Haifa
authors.initials: H
authors.lastname: Hong
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine Shanghai, China.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Qiu
keywords: Akt; HSPA12B; PI3K; PPARγ; eNOS; myocardium ischemic/reperfusion injury