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Mibefradil Suppresses the Proliferation of Pulmonary Artery Smooth Muscle Cells
SUNLONG BIOTECH / 2024-01-09
  • Author:Li, H. H., Xie, L. J., Xiao, T. T., Huang, M. & Shen, J.

  • Periodical:Journal of investigative medicine : the official publication of the American Federation for Clinical Research 64, 45-49 (2016)

  • Article source

Intracellular Ca(2+) 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 Ca(2+) channel antagonists are useful in only few patients with PAH. The present study sought to assess the effect of mibefradil, which blocks T-type Ca(2+) channels, on PASMC proliferation and Ca(2+) channel profile. Human PASMCs were stimulated with 25?ng/mL platelet-derived growth factor-BB (PDGF-BB) with and without 10??M mibefradil or 100?nM sildenafil. After 48 or 72?h, PASMC proliferation and Ca(2+) 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 Ca(2+) 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.

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