Endothelin-1 (1-31):: From chymase-dependent synthesis to cardiovascular pathologies

被引：28

作者：

D'Orleans-Juste, P. ^{[1
]}

Houde, M. ^{[1
]}

Rae, G. A. ^{[3
]}

Bkaily, G. ^{[2
]}

Carrier, E. ^{[1
]}

Simard, E. ^{[1
]}

机构：

[1] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Pharmacol, Sherbrooke, PQ J1H 5N4, Canada

[2] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Anat & Cell Biol, Sherbrooke, PQ J1H 5N4, Canada

[3] Univ Fed Santa Catarina, Dept Pharmacol, Florianopolis, SC, Brazil

来源：

VASCULAR PHARMACOLOGY | 2008年 / 49卷 / 2-3期

基金：

加拿大健康研究院;

关键词：

endothelin-1 (1-31); big-endothelin-1; chymase; endothelin-converting enzyme; neutral endopeptidase 24-11;

D O I：

10.1016/j.vph.2008.06.007

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The mast cell-derived serine protease chymase is importantly involved not only in degradation, but in synthesis of bioactive peptides as well. Several studies suggest that chymase is the predominant enzyme in the production of angiotensin II (Ang II) from angiotensin-1 in interstitial tissues. Interestingly, chymase has also been suggested to mature endothelin-1 (ET-1) from its precursor, big-ET-1 in vitro. The lack of availability of specific chymase inhibitors, beyond the chymotrypsin-like inhibitor chymostatin, currently hampers the investigation of the chymase/ET-1/Ang II paradigm in physiology and cardiovascular diseases. Nonetheless, the recent advent of highly selective chymase inhibitors is shedding new light on the role of this enzymatic pathway in the several inflammatory prone vascular diseases as summarized in the present review. Considering increasing evidence towards significant interactions between Ang II and ET-1 in cardiovascular diseases, the present review will address the role of chymase in the production of those two peptides. Whether chymase-dependent production of ET-I plays an important role in cardiovascular pathologies will also be discussed. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：51 / 62

页数：12

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