Abstract P303: Panaxnotogensengsaponins Promotes Angiogenesis and Enhances the Buildup of Effective Coronary Collateral Circulation in Ischemic Myocardium

Abstract

Background: Ischemic heart disease (IHD) is a condition that the blood vessels are narrowed or blocked due to the deposition of cholesterol plaques on the blood vessel walls. This affects the supply of blood to the heart and reduces the supply of oxygen and nutrients to the heart musculature, which has been regarded as the largest threat to the public health worldwide. PNS is a purified natural product extract that has been proved effective and widely used clinically in preventing and treating IHD in China. However, the detailed mechanisms of action of PNS remain to be addressed. The present study aims to explore the effect of PNS on modulating angiogenesis in vitro and in vivo to better understand its mechanism of action in treating IHD. Methods and Results: In this study, myocardial ischemia rat model and endothelial cell derived from human capillary blood vessel (ECV304) were utilized. Our data revealed that PNS significantly increased capillary blood vessel density in isoproterenol-induced rat ischemic myocardium model. It also decreased the pathological damage and ameliorated the ultrastructure of myocardial cells in rat ischemic myocardium as assessed by light microscopy, transmission electron microscopy and immunohistochemistry. At cellular level, PNS significantly decreased the number of apoptotic cells in rat ischemic myocardium model. Mechanistic study utilizing microarray and real-time PCR were further performed to examine the gene expression profile. The data revealed that PNS significantly upregulated the mRNA expression of a panel of angiogenic growth factors and their receptors such as VEGF, VEGFR2 and FGFR1. In vitro study revealed that PNS did not exhibit significant effect on the proliferation of ECV304 cells under normoxia culture condition; however, it facilitated the proliferation of ECV304 cells under hypoxia condition, suggesting the selective effect of PNS on angiogenesis under ischemic/hypoxic conditions. Conclusions: Our study demonstrated for the first time that PNS exerts its therapeutic effect on IHD through the mechanisms that in part involve regulating the expression of important angiogenic growth factor, which coordinately enhance the build-up of effective coronary collateral circulation in ischemic myocardium.