Enhanced store-operated Ca 2+ entry and TRPC channel expression in pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats

Xiao Ru Liu, Ming Fang Zhang, Na Yang, Qing Liu, Rui Xing Wang, Yuan Ning Cao, Xiao Ru Yang, James Sham, Mo Jun Lin

Research output: Contribution to journalArticle

Abstract

Pulmonary hypertension (PH) is associated with profound vascular remodeling and alterations in Ca 2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Previous studies show that canonical transient receptor potential (TRPC) genes are upregulated and storeoperated Ca 2+ entry (SOCE) is augmented in PASMCs of chronic hypoxic rats and patients of pulmonary arterial hypertension (PAH). Here we further examine the involvement of TRPC and SOCE in PH with a widely used rat model of monocrotaline (MCT)-induced PAH. Rats developed severe PAH, right ventricular hypertrophy, and significant increase in store-operated TRPC1 and TRPC4 mRNA and protein in endothelium-denuded pulmonary arteries (PAs) 3 wk after MCT injection. Contraction of PA and Ca 2+ influx in PASMC evoked by store depletion using cyclopiazonic acid (CPA) were enhanced dramatically, consistent with augmented SOCE in the MCT-treated group. The time course of increase in CPA-induced contraction corresponded to that of TRPC1 expression. Endothelin-1 (ET-1)- induced vasoconstriction was also potentiated in PAs of MCT-treated rats. The response was partially inhibited by SOCE blockers, including Gd 3+, La 3+, and SKF-96365, as well as the general TRPC inhibitor BTP-2, suggesting that TRPC-dependent SOCE was involved. Moreover, the ET-1-induced contraction and Ca 2+ response in the MCT group were more susceptible to the inhibition caused by the various SOCE blockers. Hence, our study shows that MCTinduced PAH is associated with increased TRPC expression and SOCE, which are involved in the enhanced vascular reactivity to ET-1, and support the hypothesis that TRPC-dependent SOCE is an important pathway for the development of PH.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume302
Issue number1
DOIs
StatePublished - Jan 2012

Fingerprint

Monocrotaline
Pulmonary Hypertension
Pulmonary Artery
Lung
Endothelin-1
Smooth Muscle Myocytes
1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
Right Ventricular Hypertrophy
Vasoconstriction
Endothelium
Blood Vessels
Homeostasis
Messenger RNA
Injections

Keywords

  • Canonical transient receptor potential 1
  • Endothelin-1
  • Monocrotaline
  • Pulmonary hypertension
  • Store-operated calcium channels

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Enhanced store-operated Ca 2+ entry and TRPC channel expression in pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats. / Liu, Xiao Ru; Zhang, Ming Fang; Yang, Na; Liu, Qing; Wang, Rui Xing; Cao, Yuan Ning; Yang, Xiao Ru; Sham, James; Lin, Mo Jun.

In: American Journal of Physiology - Cell Physiology, Vol. 302, No. 1, 01.2012.

Research output: Contribution to journalArticle

Liu, Xiao Ru ; Zhang, Ming Fang ; Yang, Na ; Liu, Qing ; Wang, Rui Xing ; Cao, Yuan Ning ; Yang, Xiao Ru ; Sham, James ; Lin, Mo Jun. / Enhanced store-operated Ca 2+ entry and TRPC channel expression in pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats. In: American Journal of Physiology - Cell Physiology. 2012 ; Vol. 302, No. 1.
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abstract = "Pulmonary hypertension (PH) is associated with profound vascular remodeling and alterations in Ca 2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Previous studies show that canonical transient receptor potential (TRPC) genes are upregulated and storeoperated Ca 2+ entry (SOCE) is augmented in PASMCs of chronic hypoxic rats and patients of pulmonary arterial hypertension (PAH). Here we further examine the involvement of TRPC and SOCE in PH with a widely used rat model of monocrotaline (MCT)-induced PAH. Rats developed severe PAH, right ventricular hypertrophy, and significant increase in store-operated TRPC1 and TRPC4 mRNA and protein in endothelium-denuded pulmonary arteries (PAs) 3 wk after MCT injection. Contraction of PA and Ca 2+ influx in PASMC evoked by store depletion using cyclopiazonic acid (CPA) were enhanced dramatically, consistent with augmented SOCE in the MCT-treated group. The time course of increase in CPA-induced contraction corresponded to that of TRPC1 expression. Endothelin-1 (ET-1)- induced vasoconstriction was also potentiated in PAs of MCT-treated rats. The response was partially inhibited by SOCE blockers, including Gd 3+, La 3+, and SKF-96365, as well as the general TRPC inhibitor BTP-2, suggesting that TRPC-dependent SOCE was involved. Moreover, the ET-1-induced contraction and Ca 2+ response in the MCT group were more susceptible to the inhibition caused by the various SOCE blockers. Hence, our study shows that MCTinduced PAH is associated with increased TRPC expression and SOCE, which are involved in the enhanced vascular reactivity to ET-1, and support the hypothesis that TRPC-dependent SOCE is an important pathway for the development of PH.",
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AU - Liu, Xiao Ru

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AU - Liu, Qing

AU - Wang, Rui Xing

AU - Cao, Yuan Ning

AU - Yang, Xiao Ru

AU - Sham, James

AU - Lin, Mo Jun

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N2 - Pulmonary hypertension (PH) is associated with profound vascular remodeling and alterations in Ca 2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Previous studies show that canonical transient receptor potential (TRPC) genes are upregulated and storeoperated Ca 2+ entry (SOCE) is augmented in PASMCs of chronic hypoxic rats and patients of pulmonary arterial hypertension (PAH). Here we further examine the involvement of TRPC and SOCE in PH with a widely used rat model of monocrotaline (MCT)-induced PAH. Rats developed severe PAH, right ventricular hypertrophy, and significant increase in store-operated TRPC1 and TRPC4 mRNA and protein in endothelium-denuded pulmonary arteries (PAs) 3 wk after MCT injection. Contraction of PA and Ca 2+ influx in PASMC evoked by store depletion using cyclopiazonic acid (CPA) were enhanced dramatically, consistent with augmented SOCE in the MCT-treated group. The time course of increase in CPA-induced contraction corresponded to that of TRPC1 expression. Endothelin-1 (ET-1)- induced vasoconstriction was also potentiated in PAs of MCT-treated rats. The response was partially inhibited by SOCE blockers, including Gd 3+, La 3+, and SKF-96365, as well as the general TRPC inhibitor BTP-2, suggesting that TRPC-dependent SOCE was involved. Moreover, the ET-1-induced contraction and Ca 2+ response in the MCT group were more susceptible to the inhibition caused by the various SOCE blockers. Hence, our study shows that MCTinduced PAH is associated with increased TRPC expression and SOCE, which are involved in the enhanced vascular reactivity to ET-1, and support the hypothesis that TRPC-dependent SOCE is an important pathway for the development of PH.

AB - Pulmonary hypertension (PH) is associated with profound vascular remodeling and alterations in Ca 2+ homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Previous studies show that canonical transient receptor potential (TRPC) genes are upregulated and storeoperated Ca 2+ entry (SOCE) is augmented in PASMCs of chronic hypoxic rats and patients of pulmonary arterial hypertension (PAH). Here we further examine the involvement of TRPC and SOCE in PH with a widely used rat model of monocrotaline (MCT)-induced PAH. Rats developed severe PAH, right ventricular hypertrophy, and significant increase in store-operated TRPC1 and TRPC4 mRNA and protein in endothelium-denuded pulmonary arteries (PAs) 3 wk after MCT injection. Contraction of PA and Ca 2+ influx in PASMC evoked by store depletion using cyclopiazonic acid (CPA) were enhanced dramatically, consistent with augmented SOCE in the MCT-treated group. The time course of increase in CPA-induced contraction corresponded to that of TRPC1 expression. Endothelin-1 (ET-1)- induced vasoconstriction was also potentiated in PAs of MCT-treated rats. The response was partially inhibited by SOCE blockers, including Gd 3+, La 3+, and SKF-96365, as well as the general TRPC inhibitor BTP-2, suggesting that TRPC-dependent SOCE was involved. Moreover, the ET-1-induced contraction and Ca 2+ response in the MCT group were more susceptible to the inhibition caused by the various SOCE blockers. Hence, our study shows that MCTinduced PAH is associated with increased TRPC expression and SOCE, which are involved in the enhanced vascular reactivity to ET-1, and support the hypothesis that TRPC-dependent SOCE is an important pathway for the development of PH.

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