Andrographolide improves the dysfunction of endothelial progenitor cells from angiotensin II-induced hypertensive mice through SIRT1 signaling

Abstract

Endothelial progenitor cells (EPCs) are crucial for the maintenance of vascular homeostasis. The dysfunction of EPCs contributes to the endothelial damage in hypertension. Andrographolide (AGP) is a traditional Chinese patent medicine that has been reported to have protective effects on cardiovascular system. However, the effect of AGP on the function of EPCs in hypertension remains unknown. In this study, we aimed to elucidate the effect of AGP on EPCs and the underlying mechanisms. In vivo, the blood pressure and endothelial function (indicated by endothelial dependent vasodilation) of AGP-fed angiotensin II (Ang II)-infused hypertensive mice were examined. In vitro, the function of EPCs isolated from bone marrow were evaluated by tube formation, migration, and adhesion assay. Additionally, a silent information regulator 1 (SIRT1) inhibitor/agonist and a small interfering RNA (si-RNA) targeting SIRT1 were used to determine the pathway involved. The results showed that AGP not only reduced blood pressure, improved endothelial function in hypertensive mice but also restored the dysfunction of EPCs of hypertension in vitro. Mechanistically, AGP up-regulated SIRT1 expression, decreased the Bax/Bcl-2 ratio and the expression level of Cleaved caspase-3, thus inhibiting the apoptosis of Ang II induced EPCs. However, the beneficial effects of AGP on EPCs disappeared after the inhibition or the knockdown of SIRT1. To summarize, this study demonstrates for the first time that AGP improves the dysfunction of EPCs through SIRT1-mediated anti-apoptotic effects. Our findings might provide a novel therapeutic strategy for treating vascular damage in hypertension.

Keywords: Andrographolide; Angiotensin II; Endothelial progenitor cells; Hypertension; SIRT1 signaling.