Differential mechanisms of angiotensin II and PDGF-BB on migration and proliferation of coronary artery smooth muscle cells

Abstract

Angiotensin II (Ang II) and platelet-derived growth factor-BB (PDGF-BB) are associated with excessive cell migration, proliferation and many growth-related diseases. However, whether these agents utilise similar mechanisms to trigger vascular pathologies remain to be explored. The effects of Ang II and PDGF-BB on coronary artery smooth muscle cell (CASMC) migration and proliferation were investigated via Dunn chemotaxis assay and the measurement of [ 3 H]thymidine incorporation rates, respectively. Both atherogens produced similar degrees of cell migration which were dramatically inhibited by mevastatin (10 nM).However, the inhibitory effects of losartan (10 nM) and MnTBAP (a free radical scavenger; 50M) were found to be unique to Ang II-mediated chemotaxis. In contrast, MnTBAP, apocynin (an antioxidant and phagocytic NADPH oxidase inhibitor; 500 µM), mevastatin and pravastatin (100 nM) equally suppressed both Ang II and PDGF-BB-induced cellular growth.Although atherogens produced similar changes in NADPH oxidase, NOS and superoxide dismutase activities, they differentially regulated antioxidant glutathione peroxidase activity which was diminished by Ang II and unaffected by PDGF-BB. Studies with signal transduction pathway inhibitors revealed the involvement of multiple pathways i.e. protein kinase C, tyrosine kinase and MAPK in Ang II-and/or PDGF-BB-induced aforementioned enzyme activity changes. In conclusion, Ang II and PDGF-BB may induce coronary atherosclerotic disease formation by stimulating CASMC migration and proliferation through agent-specific regulation of oxidative status and utilisation of different signal transduction pathways.

4-Fluoro-2-methoxyphenol, an apocynin analog with enhanced inhibitory effect on leukocyte oxidant production and phagocytosis

“…In other words, TNFα release inhibition by apocynin or F-apocynin does not seem to be a result of the redox imbalance resulting from NADPH oxidase activity inhibition. Recently, Dharmarajah et al (2010) showed that the anti-platelet actions of apocynin are not the result of an inhibitory effect on NADPH oxidase or reactive oxygen species scavenging, as proposed by others (Allen and Bayraktutan, 2008), and suggested that this effect reinforces the indication of this drug as an antithrombotic agent. It confirms that the effects of apocynin extend beyond NADPH oxidase inhibition and consequent redox imbalance.…”

Manganese superoxide dismutase inhibits neointima formation through attenuation of migration and proliferation of vascular smooth muscle cells

“…Ang II is a main biologically active agent of the renin–angiotensin system and plays an important role in the migration of VSMCs, which contributes to restenosis after vascular injury [17,26,28]. To explore the mechanisms by which SOD2 inhibits intimal hyperplasia, we used a wound healing assay to evaluate the effect of SOD2 on Ang II-stimulated VSMC migration.…”

Effect of angiotensin ii type 1 receptor antagonist, losartan on inflammatory factor in atherosclerotic rabbits

“…Losartan may be acting on inhibiting protein of nuclear factor κB and lead MCP-1, VCAM-1, E-selection in adhesion process to reduce, inhibiting the inflammatory response in occurrence of atherosclerosis ( 15 , 16 ). Hence, further study is required to be done.…”