Monocyte chemoattractant protein-1 mediates angiotensin II-induced vascular smooth muscle cell proliferation via SAPK/JNK and ERK1/2

Abstract

Abnormal vascular smooth muscle cells proliferation is the pathophysiological basis of cardiovascular diseases, such as hypertension, atherosclerosis, and restenosis after angioplasty. Angiotensin II can induce abnormal proliferation of vascular smooth muscle cells, but the molecular mechanisms of this process remain unclear. Here, we explored the role and molecular mechanism of monocyte chemotactic protein-1, which mediated angiotensin II-induced proliferation of rat aortic smooth muscle cells. 1,000 nM angiotensin II could stimulate rat aortic smooth muscle cells' proliferation by angiotensin II type 1 receptor (AT(1)R). Simultaneously, angiotensin II increased monocyte chemotactic protein-1 expression and secretion in a dose-and time-dependent manner through activation of its receptor AT(1)R. Then, monocyte chemotactic protein-1 contributed to angiotensin II-induced cells proliferation by CCR2. Furthermore, we found that intracellular ERK and JNK signaling molecules were implicated in angiotensin II-stimulated monocyte chemotactic protein-1 expression and proliferation mediated by monocyte chemotactic protein-1. These results contribute to a better understanding effect on angiotensin II-induced proliferation of rat smooth muscle cells.

Histone deacetylase inhibitor-temozolomide co-treatment inhibits melanoma growth through suppression of Chemokine (C-C motif) ligand 2-driven signals

“…The available evidence supports that CCL2, a chemotactic factor for monocytes and T lymphocytes plays key roles in tumorigenesis promotion in different tumor types [30, 31]. Intracellular JNK-signaling is implicated in CCL2 expression and CCL2-mediated proliferation [31, 32].…”

“…Intracellular JNK-signaling is implicated in CCL2 expression and CCL2-mediated proliferation [31, 32]. Consistently, cells lacking JNK1/2 were shown to display reduced levels of ccl2 mRNA [33].…”

The Role of Chemokines in Hypertension

“…elevated MCP-1 expression has been observed in atherosclerosis and angina pectoris, including unstable angina [5], both in animal models and in clinical trials. by activating CCR2, angiotensin II stimulates proliferation of the smooth muscle cells of the aorta, which is a significant process in the pathogenesis of hypertension, arteriosclerosis and vascular stent restenosis [6]. a lack of functional CCR5 and CCR2 receptors may be associated with the emergence of hypertension [7].…”

The C4280A (rs5705) gene polymorphism of the renin (REN) gene is associated with risk of developing coronary artery disease, but not with restenosis after coronary stenting

“…In the literature, there has been evidence that the activation of the renin-angiotensin system (RAS) induces the production of pro-inflammatory cytokines, proliferation and vasoconstriction on the vasculature, and in consequence can contribute to initiation and progression of atherosclerosis (Chamarthi et al, 2011;Mehta and Griendling, 2007;van Thiel et al, 2015;Pacurari et al, 2014). In addition, RAS has been implicated in the pathogenesis of neointimal hyperplasia, and a role for angiotensin II in the migration and proliferation of vascular smooth muscle cells in restenosis has been reported (Pacurari et al, 2014;Valente et al, 2012;Yao et al, 2012). Renin and angiotensinogen are encoded by the REN and AGT genes located in chromosome 1 position q32 and q42, respectively (Qin et al, 1993;Gaillard-Sanchez et al, 1990).…”