Impact of phosphatidylinositide 3-kinase signaling pathway on the cardioprotection induced by intermittent hypoxia

G Milano,P.M Abruzzo,A Bolotta,M Marini,L Terraneo,B Ravara,L Gorza,L.K Von Segesser,M Samaja

doi:10.1016/j.atherosclerosis.2014.05.838

Abstract

Background: Exposure to intermittent hypoxia (IH) may enhance cardiac function and protects heart against ischemia-reperfusion (I/R) injury. To elucidate the underlying mechanisms, we developed a cardioprotective IH model that was characterized at hemodynamic, biochemical and molecular levels.

Highlights

Ischemic preconditioning (IP), term used to identify the phenomenon whereby repeated exposures to sub-lethal ischemia episodes enhance myocardial protection against potentially lethal ischemia [1], probably still represents the best tool for efficient prevention strategy against cardiovascular diseases
IP is a potentially powerful and economic approach to reduce the burden of myocardial ischemia disease, several bottlenecks prevent its usability in humans
The intermittent hypoxia (IH) protocol described here enabled hearts to improve performance, induce neo-angiogenesis, increase the expression of HO-1 and decrease that of CHOP, indicative of attenuated apoptosis induced by endoplasmic reticulum stress

Summary

Introduction

Ischemic preconditioning (IP), term used to identify the phenomenon whereby repeated exposures to sub-lethal ischemia episodes enhance myocardial protection against potentially lethal ischemia [1], probably still represents the best tool for efficient prevention strategy against cardiovascular diseases. Mice were anesthetized and subdivided in various subgroups for analysis of contractility (pressure-volume loop), morphology, biochemistry or resistance to I/R (30-min occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion and measurement of the area at risk and infarct size). Results: We found that IH did not induce myocardial hypertrophy; rather both contractility and cardiac function improved with greater number of capillaries per unit volume and greater expression of VEGF-R2, but not of VEGF. Besides increasing the phosphorylation of protein kinase B (Akt) and the endothelial isoform of NO synthase with respect to control, IH reduced the infarct size and post-LAD proteins carbonylation, index of oxidative damage. Conclusion: We conclude that the PI3K/Akt pathway is crucial for IH-induced cardioprotection and may represent a viable target to reduce myocardial I/R injury

Objectives

Results

Conclusion