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GW24-e2208 Dopamine D1-like receptors suppress proliferation of vascular smooth muscle cell induced by insulin-like growth factor-1
  1. Kou Xun1,2,
  2. Yu Han1,2,
  3. Di Yang1,2,
  4. Jinjuan Fu1,2,
  5. Shuo Zheng1,2,
  6. Duofen He1,2,
  7. Lin Zhou1,2,
  8. Chunyu Zeng1,2
  1. 1Department of Cardiology, Daping Hospital, The Third Military Medical University
  2. 2Chongqing Institute of Cardiology, Chongqing, PR China

Abstract

Objectives Proliferation of vascular smooth muscle cells (VSMCs) participates in the pathogenesis and development of cardiovascular diseases, including essential hypertension and atherosclerosis. Our previous study found that stimulation of D1-like dopamine receptors inhibited insulin-induced proliferation of VSMCs. Insulin-like growth factor-1 (IGF-1) and insulin share similar structure and biological effect. However, whether or not there is any effect of D1-like receptors on IGF-1-induced proliferation of VSMCs is not known. Therefore, we investigated the inhibitory effect of D1-like dopamine receptors on the IGF-1-induced VSMCs proliferation in this study.

Methods VSMC proliferation was determined by [3H]-thymidinein corporation, the uptake of 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and cell number. Phosphorylated/non-phosphorylated IGF-1 receptor, Akt, mTOR and p70S6K expressions were determined by immunoblotting. The oligodeoxynucleotides were transfected to A10 cells to identify the effect of D1 and D5 receptors respectively.

Results IGF-1 increased the proliferation of VSMCs, while in the presence of fenoldopam, IGF-1 mediated stimulatory effect was reduced. Use of either the antisense for D1 or D5 receptor partially inhibited the fenoldopam-induced anti-proliferation effect of VSMCs. Use of both D1 andD5 receptor antisenses completely blocked the inhibitory effect of fenoldopam. In the presence of PI3k and mTOR inhibitors, the IGF-1 mediated proliferation of VSMCs was blocked. Moreover, IGF-1 increased the phosphorylation of PI3k and mTOR. The inhibitory effect of fenoldopam on VSMC proliferation might be due to the inhibition of IGF-1 receptor expression and IGF-1 phosphorylation, since in the presence offenoldopam, the stimulatory effect of IGF-1 on phosphorylation of IGF-1 receptor, PI3k and mTOR is reduced, the IGF-1 receptor expression was reducedin A10 cells.

Conclusions Activation of the D1-like receptors suppressed the proliferative effect of IGF-1 in A10 cells via the inhibition of the IGF-1R/Akt/mTOR/p70S6K pathway.

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