期刊
CIRCULATION RESEARCH
卷 122, 期 2, 页码 319-336出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.117.310978
关键词
angiotensin II; chymases; endothelial cells; mast cells; renin
资金
- Department of Veteran Affairs for Merit Review [1CX000993-01, 1BX003664-01]
- National Institutes of Health [P01 HL051952]
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.
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