Key result
Asymmetric dimethylarginine (ADMA) induces vascular smooth muscle cell migration and phenotype change via activation of the Rho/ROCK signaling pathway, which is reversed by ROCK inhibition.
Why the study?
Does ADMA induce vascular smooth muscle cell migration and phenotype change via the Rho/ROCK signaling pathway?
Does ADMA induce vascular smooth muscle cell migration and phenotype change via the Rho/ROCK signaling pathway?
ADMA induces vascular smooth muscle cell migration and phenotype change via the Rho/ROCK signaling pathway, providing potential mechanistic insights into atherosclerosis development and therapy.
Hypothesis-generating for ADMA in vascular remodeling; leaves open therapeutic relevance pending in vivo validation.
Asymmetric dimethylarginine (ADMA) induces vascular smooth muscle cells (VSMCs) migration. VSMC phenotype change is a prerequisite of migration. RhoA and Rho-kinase (ROCK) mediate migration of VSMCs. We hypothesize that ADMA induces VSMC migration via the activation of Rho/ROCK signal pathway and due to VSMCs phenotype change. ADMA activates Rho/ROCK signal pathway that interpreted by the elevation of RhoA activity and phosphorylation level of a ROCK substrate. Pretreatment with ROCK inhibitor, Y27632 completely reverses the induction of ADMA on ROCK and in turn inhibits ADMA-induced VSMCs migration. When the Rho/ROCK signal pathway has been blocked by pretreatment with Y27632, the induction of ERK signal pathway by ADMA is completely abrogated. Elimination of ADMA via overexpression of dimethylarginine dimethylaminohydrolase 2 (DDAH2) and L-arginine both blocks the effects of ADMA on the activation of Rho/ROCK and extra cellular signal-regulated kinase (ERK) in VSMCs. The expression of differentiated phenotype relative proteins was reduced and the actin cytoskeleton was disassembled by ADMA, which were blocked by Y27632, further interpreting that ADMA inducing VSMCs migration via Rho/ROCK signal pathway is due to its effect on the VSMCs phenotype change. Our present study may help to provide novel insights into the therapy and prevention of atherosclerosis.
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Zhou et al. (2014) studied Atherosclerosis. Asymmetric dimethylarginine (ADMA) was evaluated on Vascular smooth muscle cell (VSMC) migration and phenotype change. Asymmetric dimethylarginine (ADMA) induces vascular smooth muscle cell migration and phenotype change via activation of the Rho/ROCK signaling pathway, which is reversed by ROCK inhibition.
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