Upregulation of canonical transient receptor potential channel in the pulmonary arterial smooth muscle of a chronic thromboembolic pulmonary hypertension rat model

Xin Yun, Yuqin Chen, Kai Yang, Sabrina Wang, Wenju Lu, Jian Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Chronic ligation of the left main pulmonary artery (PA) results in pulmonary vascular remodeling and sustained vasoconstriction. This method has been used to generate a postobstructive pulmonary vasculopathy model to mimic severe chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to examine the cellular and molecular mechanisms underlying CTEPH and to provide evidence for potential treatments. The CTEPH rat model was induced by surgical left PA ligation (LPAL). Right ventricular systolic pressure (RVSP), lung histochemistry and plasma D-dimer measurements were carried out to evaluate the model. A fluorescence microscope was used to measure the basal intracellular Ca 2+ concentration ([Ca 2+ ] i) and store-operated Ca 2+ entry (SOCE) in rat distal pulmonary arterial smooth muscle cells through a Fura-2 fluorescence-based method. The expression of the canonical transient receptor potential channel 1 (TRPC1) and TRPC6 was determined by western blotting and real-time quantitative PCR in isolated distal pulmonary arteries (PA). At the time points of 2 and 5 weeks postsurgery, the RVSP showed significant increases in the LPAL groups in comparison with the respective control groups. LPAL also led to right ventricular hypertrophy (RVH), distal pulmonary arterial remodeling in unobstructed territories and persistently higher plasma D-dimer levels. Increases of the basal [Ca 2+ ] i and SOCE in LPAL were associated with a clear upregulation of TRPC1 and TRPC6 expression in the distal PA. Our study demonstrated that LPAL successfully reproduced the vascular tone changes that mimic CTEPH pathogenesis. In this model, the increased RVSP and RVH are likely related to enhanced SOCE and upregulated TRPC1 and TRPC6 expression levels in the distal PA.

Original languageEnglish (US)
Pages (from-to)821-828
Number of pages8
JournalHypertension Research
Volume38
Issue number12
DOIs
StatePublished - Dec 1 2015

Keywords

  • SOCE
  • TRPC
  • chronic thromboembolic pulmonary hypertension (CTEPH)
  • pulmonary artery ligation

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

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