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Dependence of Cathepsin L –induced Coronary Endothelial Dysfunction upon Activation of NAD(P)H Oxidase
Author(s) -
Zhang Fan,
Zhang Andrew Y,
Li PinLan
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.937.6
Subject(s) - endostatin , chemistry , bradykinin , cathepsin , endothelial dysfunction , coronary arteries , endothelium , endocrinology , medicine , microbiology and biotechnology , angiogenesis , biochemistry , enzyme , artery , biology , receptor
Cathepsin L can generate endogenous endostatin in vascular and epithelial basement. The present study was designed to determine whether and how this cathepsin L‐derived endogenous endostatin alters endothelium‐dependent vasodilator responses in coronary arteries. In isolated and perfused small bovine coronary arteries, cathepsin L (200 ng/ml) markedly attenuated endothelium‐dependent vasodilator responses to bradykinin or A23187 by 56.16±9.58% and 68.95±10.32%, respectively. This inhibitory effect could be significantly reversed by pre‐treatment with O 2 −. scavenger, tiron, or anti‐endostatin antibody. ELISA assay revealed that cathepsin L dose dependently increased endostatin production in coronary arteries. In situ fluorescent microscopic imaging showed that cathepsin L decreased bradykinin‐ and A23187‐induced NO production in the intact endothelium, but with no effect on Ca 2+ response. This cathepsin L‐induced reduction of NO was restored by the pretreatment of an anti‐endostatin antibody and tiron. Electron spin resonance (ESR) analysis demonstrated that cathepsin L increased O 2 −. production, which could be markedly attenuated by apocynin or anti‐endostatin antibody. It is concluded that endostatin could be endogenously produced in coronary arteries, which may result in endothelial dysfunction by NADPH oxidase activation (Supported by NIH grants HL57244, HL075316, and DK54927).