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Circ Res. 2018 Jan 19;122(2):319-336. doi: 10.1161/CIRCRESAHA.117.310978.

Multifunctional Role of Chymase in Acute and Chronic Tissue Injury and Remodeling.

Author information

1
From the Department of Medicine, Division of Cardiology, Birmingham Veteran Affairs Medical Center (L.J.D.), Division of Cardiovascular Disease, Department of Medicine (L.J.D.), and Department of Cell, Developmental and Integrative Biology (J.F.C.), University of Alabama at Birmingham; and Division of Surgical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (C.M.F.). louis.dellitalia@va.gov.
2
From the Department of Medicine, Division of Cardiology, Birmingham Veteran Affairs Medical Center (L.J.D.), Division of Cardiovascular Disease, Department of Medicine (L.J.D.), and Department of Cell, Developmental and Integrative Biology (J.F.C.), University of Alabama at Birmingham; and Division of Surgical Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (C.M.F.).

Abstract

Chymase is the most efficient Ang II (angiotensin II)-forming enzyme in the human body and has been implicated in a wide variety of human diseases that also implicate its many other protease actions. Largely thought to be the product of mast cells, the identification of other cellular sources including cardiac fibroblasts and vascular endothelial cells demonstrates a more widely dispersed production and distribution system in various tissues. Furthermore, newly emerging evidence for its intracellular presence in cardiomyocytes and smooth muscle cells opens an entirely new compartment of chymase-mediated actions that were previously thought to be limited to the extracellular space. This review illustrates how these multiple chymase-mediated mechanisms of action can explain the residual risk in clinical trials of cardiovascular disease using conventional renin-angiotensin system blockade.

KEYWORDS:

angiotensin II; chymases; endothelial cells; mast cells; renin

PMID:
29348253
PMCID:
PMC5776735
[Available on 2019-01-19]
DOI:
10.1161/CIRCRESAHA.117.310978

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