Geranylgeranylacetone attenuates myocardium ischemic/reperfusion injury through HSP70 and Akt/GSK-3β/eNOS pathway.
Early reperfusion of myocardial infarction area is the most effective and important therapy to acute myocardial infarction, but could induce reperfusion injury. Geranylgeranylacetone (GGA), an acyclic polyisoprenoid used as an oral anti-ulcer medication, has been reported to have protective effects on reperfusion injury. In the present study, we explored the protective effect of GGA against MIRI and the underlying mechanism. We pretreated rats with four daily GGA, and then observed its effects on heart function parameters following in situ ischemia/reperfusion. GGA exhibited dramatic improvement in cardiac functions, as manifested by increased LVSP and ± (dP/dt) max and decreased LVDP. Oxidative injury and inflammatory response were also relieved by GGA. Western blot showed that the HSP70 protein expression and the Akt/GSK-3β/eNOS pathway were activated. The inhibition of HSP70 and the Akt/GSK-3β/eNOS pathway significantly reversed the protective effects of GGA on MIRI, indicating the involvements of HSP70 and the Akt/GSK-3β/eNOS pathway.
Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine Shanghai, China.
Chunxia
C
Zhou
Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine Shanghai, China.
Jie
J
Bai
Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine Shanghai, China.
Chuan
C
Jiang
Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine Shanghai, China.
Lincai
L
Ye
Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine Shanghai, China.
Yanjun
Y
Pan
Department of Thoracic and Cardiovascular Surgery, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine Shanghai, China.
Haibo
H
Zhang
Akt/GSK-3β/eNOS; HSP70; Myocardium ischemic/reperfusion injury; geranylgeranylacetone