Abstract
Adiponectin is an anti-atherogenic adipokine that inhibits the development of plaque by mechanisms that are not completely understood. Extracellular matrix (ECM) may have a role in the pathogenesis of atherosclerosis. We explored the effect and mechanisms of adiponectin on the synthesis of prolyl-4-hydroxylase (P4H) in interleukin 6 (IL-6)-stimulated human aortic smooth muscle cells (HASMCs). P4Hα1 mRNA level was quantified by RT-PCR, the protein levels of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and P4Hα1 were quantified by western blot analysis, and activation of specific protein 1 (Sp1) was determined by electrophoretic mobility shift assay and subcellular localization of Sp1 by immunofluorescence analysis. Adiponectin significantly increased P4Hα1 mRNA and protein levels in IL-6-stimulated HASMCs in a dose- and time-dependent manner. As well, ERK1/2 and Sp1 played a crucial role in the effect of adiponectin upregulating P4Hα1 expression in IL-6-stimulated HASMCs. Adiponectin abrogated the effects of IL-6 on collagen III level, which may indicate that P4Hα1 is essential for folding the procollagen polypeptide chains into stabilized collagen. Adiponectin attenuates IL-6–inhibited P4Hα1 synthesis and stabilizes collagen formation in HASMCs through a Sp1-ERK1/2-P4Hα1-dependent pathway.
Highlights
Experimental results have demonstrated that the pathogenesis of atherosclerosis is based on several mechanisms
specific protein 1 (Sp1) regulates the effect of adiponectin upregulating P4Ha1 expression in interleukin 6 (IL-6)-stimulated human aortic smooth muscle cells (HASMCs)
We aimed to investigate the role of Extracellular matrix (ECM) in the pathogenesis of atherosclerosis and the potential mechanism of adiponectin upregulating P4Ha expression in IL-6-stimulated HASMCs
Summary
Experimental results have demonstrated that the pathogenesis of atherosclerosis is based on several mechanisms. Extracellular matrix (ECM) may have a role in the pathogenesis of atherosclerosis [1]. ECM components, especially collagen, are thought to be important in the progression of atherosclerosis. Prolyl-4-hydroxylase (P4H) is a key intracellular enzyme essential for all known types of collagen maturation and secretion [2]. P4H is regulated by various cytokines, including tumor necrosis factor a, transforming growth factor b, and interleukins (ILs) [5]. IL-6 is one of the most potent cytokines involved in cardiovascular pathogenesis and actively regulates ECM metabolism [6]. Adiponectin is an adipocyte-specific plasma protein, has anti-inflammatory properties and might regulate ECM metabolism
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