The potential role of MLC phosphatase and MAPK signalling in the pathogenesis of vascular dysfunction in heart failure.

Journal of Cellular and Molecular Medicine
Ozgur Ogut, Frank V Brozovich

Abstract

The clinical syndrome of heart failure is associated with both a resting vasoconstriction and reduced sensitivity to nitric oxide mediated vasodilatation, and this review will focus on the role of myosin light chain (MLC) phosphatase in the pathogenesis of the vascular abnormalities of heart failure. Nitric oxide mediates vasodilatation by an activation of guanylate cyclase and an increase in the production of cGMP, which leads to the activation of the type I cGMP-dependent protein kinase (PKGI). PKGI then activates a number of targets that produce smooth muscle relaxation including MLC phosphatase. MLC phosphatase is a holoenzyme consisting of three subunits; a 20 kD subunit of unknown function, an approximately 38-kD catalytic subunit and a myosin targeting subunit (MYPT1). Alternative splicing of a 31 bp 3 exon generates MYPT1 isoforms, which differ by a COOH-terminus leucine zipper (LZ). Further, PKGI-mediated activation of MLC phosphatase requires the expression of a LZ+ MYPT1. Congestive heart failure is associated with a decrease in LZ+ MYPT1 expression, which results in a decrease in the sensitivity to cGMP-mediated smooth muscle relaxation. Beyond their ability to reduce afterload, angiotensin converting enzyme (ACE) i...Continue Reading

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Citations

Oct 25, 2011·Pflügers Archiv : European journal of physiology·Lei YingYuansheng Gao
Nov 23, 2012·Journal of Vascular Research·Young Soo Han, Frank V Brozovich
Oct 1, 2013·American Journal of Respiratory Cell and Molecular Biology·Luigino CalzettaAugusto Orlandi
May 7, 2011·Journal of Cellular and Molecular Medicine·Weiming LiJie Du
Jul 5, 2010·Pharmaceuticals·Naranjan S Dhalla, Alison L Müller
Jun 8, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bing ChenKaizhi Lu
Jun 6, 2018·Frontiers in Physiology·Roberto V ReyesAníbal J Llanos
Mar 13, 2021·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Yang YuCheng Xu

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