The role of pulmonary vascular contractile protein expression in pulmonary arterial hypertension

Ewa A. Konik, Young Soo Han, Frank V. Brozovich

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Pulmonary arterial hypertension (PAH) is associated with refractory vasoconstriction and impaired NO-mediated vasodilatation of the pulmonary vasculature. Vascular tone is regulated by light chain (LC) phosphorylation of both nonmuscle (NM) and smooth muscle (SM) myosins, which are determined by the activities of MLC kinase and MLC phosphatase. Further, NO mediated vasodilatation requires the expression of a leucine zipper positive (LZ. +) isoform of the myosin targeting subunit (MYPT1) of MLC phosphatase. The objective of this study was to define contractile protein expression in the pulmonary arterial vasculature and vascular reactivity in PAH. In severe PAH, compared to controls, relative LZ+MYPT1 expression was decreased (100. ±. 14% vs. 60. ±. 6%, p < 0.05, n = 7-8), and NM myosin expression was increased (15 ± 4% vs. 53. ± 5% of total myosin, p < 0.05, n = 4-6). These changes in contractile protein expression should alter vascular reactivity; following activation with Ang II, force activation and relaxation were slowed, and sustained force was increased. Further, the sensitivity to ACh-mediated relaxation was reduced. These results demonstrate that changes in the pulmonary arterial SM contractile protein expression may participate in the molecular mechanism producing both the resting vasoconstriction and the decreased sensitivity to NO-mediated vasodilatation associated with PAH.

Original languageEnglish (US)
Pages (from-to)147-155
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume65
DOIs
StatePublished - Dec 1 2013

Keywords

  • Myosin light chain phosphatase
  • Myosin phosphatase targeting subunit 1
  • Nitric oxide
  • Nonmuscle myosin
  • Smooth muscle myosin
  • Vascular reactivity

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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