Lysophosphatidic acid-induced vascular neointimal formation in mouse carotid arteries is mediated by the matricellular protein CCN1/Cyr61.

Lysophosphatidic acid-induced vascular neointimal formation in mouse carotid arteries is mediated by the matricellular protein CCN1/Cyr61.
Am J Physiol Cell Physiol. 2016 Oct 19;:ajpcell.00227.2016
Authors: Hao F, Zhang F, Wu DD, An D, Shi J, Li G, Xu X, Cui MZ
Abstract
Vascular smooth muscle cell (SMC) migration is an essential step involved in neointimal formation in restenosis and atherosclerosis. Lysophosphatidic acid (LPA) is a bioactive component of oxidized low density lipoprotein and is produced by activated platelets, implying that LPA influences vascular remodeling. Our previous study revealed that matricellular protein CCN1, a prominent extracellular matrix (ECM) protein, mediates LPA-induced SMC migration in vitro. Here we examined the role of CCN1 in LPA-induced neointimal formation. By using LPA infusion of carotid artery in a mouse model, we demonstrated that LPA highly induced CCN1 expression (6~7 fold) in neointimal lesions. Down-regulation of CCN1 expression with the specific CCN1 siRNA in carotid arteries blocked LPA-induced neointimal formation, indicating that CCN1 is essential in LPA-induced neointimal formation. We then used LPA receptor knockout (LPA1-/-, LPA2-/- and LPA3-/-) mice to examine LPA receptor function in CCN1 expression in vivo and in LPA-induced neointimal formation. Our data reveal that LPA1 deficiency, but not LPA2 or LPA3 deficiency, prevents LPA-induced CCN1 expression in vivo in mouse carotid...

Source: Am J Physiol Cell Ph... - October 18, 2016 Category: Cytology Authors: Hao F, Zhang F, Wu DD, An D, Shi J, Li G, Xu X, Cui MZ Tags: Am J Physiol Cell Physiol Source Type: research