TRPV1 activation impedes foam cell formation by inducing autophagy in oxLDL-treated vascular smooth muscle cells.

B-H Li,L Guo,C-Y Gao,Y Liu,Y Pi,J-C Li,Y-W Yin,L-L Zhang,X-J Cao

doi:10.1038/cddis.2014.146

Abstract

Vascular smooth muscle cells (VSMCs) are an important origin of foam cells besides macrophages. The mechanisms underlying VSMC foam cell formation are relatively little known. Activation of transient receptor potential vanilloid subfamily 1 (TRPV1) and autophagy have a potential role in regulating foam cell formation. Our study demonstrated that autophagy protected against foam cell formation in oxidized low-density lipoprotein (oxLDL)-treated VSMCs; activation of TRPV1 by capsaicin rescued the autophagy impaired by oxLDL and activated autophagy–lysosome pathway in VSMCs; activation of TRPV1 by capsaicin impeded foam cell formation of VSMCs through autophagy induction; activation of TRPV1 by capsaicin induced autophagy through AMP-activated protein kinase (AMPK) signaling pathway. This study provides evidence that autophagy plays an important role in VSMC foam cell formation and highlights TRPV1 as a promising therapeutic target in atherosclerosis.

Highlights

Macroautophagy, which we refer to as autophagy hereafter, is a process of ‘self-eating’ that acts as a major survival mechanism by degrading and recycling organelles and portions in cytosol.[5]
Rap rescued, whereas 3-MA exacerbated, the impaired autophagy in oxidized low-density lipoprotein (oxLDL)-treated vascular smooth muscle cells (VSMCs), manifested by the changes of LC3-II/LC3-I ratio (Figure 1d) and GFP-labeled autophagosomes (Figure 1e). Both Oil Red O staining and total cholesterol quantification showed that Rap inhibited the oxLDL-induced foam cell formation, whereas 3-MA exerted the opposite effect (Figures 1f and g). These results show that autophagy protects against foam cell formation in oxLDLtreated VSMCs
Our study demonstrated that autophagy protected against foam cell formation in oxLDL-treated VSMCs; activation of Transient receptor potential vanilloid subfamily 1 (TRPV1) by capsaicin rescued the autophagy impaired by oxLDL and activated autophagy– lysosome pathway in VSMCs; activation of TRPV1 by capsaicin impeded VSMC foam cell formation through autophagy induction; activation of TRPV1 by capsaicin induced autophagy through AMPK signaling pathway

Summary

Introduction

Macroautophagy, which we refer to as autophagy hereafter, is a process of ‘self-eating’ that acts as a major survival mechanism by degrading and recycling organelles and portions in cytosol.[5]. Lipid droplets are delivered to lysosomes and hydrolyzed to generate free cholesterol mainly for ATP-binding cassette transporter A1 (ABCA1)dependent efflux.[10] Activation of autophagy can decrease, whereas inhibition of autophagy can increase, the intracellular accumulation of total cholesterol and cholesterol esters.[11] the potential role of autophagy in the VSMC foam cell formation has been rarely reported. Transient receptor potential vanilloid subfamily 1 (TRPV1), a nonselective cation channel that is activated by capsaicin, has a protective effect against cardiovascular and cerebrovascular diseases.[12,13,14,15,16,17] TRPV1 expresses in VSMC and is found to reduce the lipid accumulation in cultured cells via increasing cholesterol efflux and reducing lipid uptake.[13] Most recently, activation of TRPV1 by capsaicin has been reported to induce autophagy in hepatocytes and mouse thymocytes.[12,18] the present study was designed to investigate potential role of autophagy in VSMC foam cell formation, and the potential effect of TRPV1 on autophagy in VSMCs challenged with oxidized low-density lipoprotein (oxLDL)

Methods

Results

Conclusion