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Mibefradil suppresses the proliferation of pulmonary artery smooth muscle cells
  1. Hong-Hong Li,
  2. Li-Jian Xie,
  3. Ting-Ting Xiao,
  4. Min Huang,
  5. Jie Shen
  1. Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China
  1. Correspondence to Jie Shen, Department of Cardiology, Shanghai Children's Hospital, Shanghai Jiaotong University, 355 Luding Road, Shanghai 200062,   People's Republic of China; she6nt{at}163.com

Abstract

Intracellular Ca2+ levels play a critical role in the regulation of vasodilation and vasoconstriction by stimulating pulmonary artery smooth muscle cell (PASMC) proliferation, which is important in the pathogenesis of pulmonary arterial hypertension (PAH); however, L-type Ca2+ channel antagonists are useful in only few patients with PAH. The present study sought to assess the effect of mibefradil, which blocks T-type Ca2+ channels, on PASMC proliferation and Ca2+ channel profile. Human PASMCs were stimulated with 25 ng/mL platelet-derived growth factor-BB (PDGF-BB) with and without 10 µM mibefradil or 100 nM sildenafil. After 48 or 72 h, PASMC proliferation and Ca2+ channel expression were assessed by MTT assays and western blot analysis, respectively. PDGF-BB-induced PASMC proliferation at 72 h (p<0.01), which was inhibited by both sildenafil and mibefradil (p<0.01). Transient receptor potential Ca2+ channel 6 (TRPC6) expression was significantly increased with PDGF-BB stimulation (p=0.009); however, no changes in TRPC1, TRPC3, CAV1.2, and CAV3.2 levels were observed. Although both TRPC1 and CAV1.2 expression levels were increased in PDGF-stimulated PASMCs on mibefradil and sildenafil treatment, it was not statistically significant (p=0.086 and 1.000, respectively). Mibefradil inhibits PDGF-BB-stimulated PASMC proliferation; however, the mechanism through which it functions remains to be determined. Further studies are required to elucidate the full therapeutic value of mibefradil for PAH.

  • Ca2+ channel
  • mibefradil
  • proliferation
  • pulmonary arterial hypertension
  • vasoconstriction

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