Inhibitory effect of Hsp70 on angiotensin II-induced vascular smooth muscle cell hypertrophy

Ying Zheng,Chang-Nim Im,Jeong-Sun Seo

doi:10.1038/emm.2006.60

Abstract

Angiotensin II (Ang II), which is an important mediator of both vascular responsiveness and growth, has been shown to induce vascular smooth muscle cell (VSMC) hypertrophy via the activation of a complex series of intracellular signaling events. Heat shock protein 70 (Hsp70) has recently been shown to protect against Ang II-induced hypertension. In this study, we tested the hypothesis that Hsp70 can protect VSMC from Ang II-induced hypertrophy. We treated VSMCs with Ang II to induce hypertrophy and to activate MAPK signaling pathway. We observed that the augmentation of Hsp70 expression inhibited Ang II-stimulated VSMC hypertrophy. This inhibitory effect of Hsp70 appears to be partly due to extracellular signal-regulated kinase (ERK1/2) inactivation, which in turn, may possibly result from the accumulation of MAP kinase phosphatase-1 (MKP-1).

Highlights

Angiotensin angiotensin II (II) (Ang II), the principal product of the renin-angiotensin system (Touyz and Berry, 2002), participates in the induction of endothelial dysfunction, vascular remodeling, and inflammation, in pathological conditions such as hypertension and atherosclerosis
Our results show that Heat shock protein 70 (Hsp70) exerts inhibitory effect on vascular smooth muscle cell (VSMC) hypertrophy via the inactivation of extracellular signal-regulated kinase 1/2 (ERK1/2), which is activated by Angiotensin II (Ang II), and that the Hsp70-mediated stabilization of MAP kinase phosphatase (MKP)-1 may be involved in this process
These results indicate that pre-induction of Hsp70 inhibits Ang II-induced VSMC hypertrophy

Summary

Introduction

Angiotensin II (Ang II), the principal product of the renin-angiotensin system (Touyz and Berry, 2002), participates in the induction of endothelial dysfunction, vascular remodeling, and inflammation, in pathological conditions such as hypertension and atherosclerosis These effects are transduced through the G-protein coupled angiotensin subtype 1 (AT-1) receptor. Ang II phosphorylates vascular p38 MAPK, which is crucial to inflammatory responses and apoptosis (Hommes et al, 2003) These signaling processes and associated cellular functions are crucial to the development of the vascular damage associated with cardiovascular diseases, including hypertension and atherosclerosis (Touyz and Schiffrin, 2000; Suzuki et al, 2004; Tojo et al, 2005). MKK3 and MKK6 selectively activate p38-MAPK in different cell types, and exhibit isoform specificity (Sugden and Clerk, 1998)

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