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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2009-6-15
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pubmed:abstractText |
Cathepsin L is a cysteine protease that can generate endogenous endostatin in vascular and epithelial basement membranes and importantly participates in a variety of pathophysiological processes. The present study was designed to determine whether this cathepsin L-derived endogenous endostatin alters endothelium-dependent vasodilator responses in coronary arteries via NAD(P)H oxidase activation. In isolated and perfused small bovine coronary arteries, administration of 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 of cathepsin L on endothelium-dependent vasodilator responses could be significantly reversed by pre-incubation of the arteries with O(2)(-) scavenger, Tiron, or neutralizing anti-endostatin antibody. By fluorescent ELISA assay, cathepsin L dose-dependently increased endostatin production in coronary arteries. In situ high-speed dual wavelength switching fluorescent microscopic imaging showed that cathepsin L decreased bradykinin- and A23187-induced NO levels in the intact endothelium, but it had no effect on Ca(2+) response to these vasodilators. This cathepsin L-induced reduction of NO was restored by the pretreatment of an anti-endostatin antibody. Electron spin resonance (ESR) analysis demonstrated that cathepsin L increased O(2)(-) production which could be markedly attenuated by the NAD(P)H oxidase inhibitors, apocynin or anti-endostatin antibody. It is concluded that endostatin could be endogenously produced in coronary arteries when cathepsin L is increased and that this cathepsin L-derived endostatin, if excessive, may result in endothelial dysfunction through enhanced production of O(2)(-) due to NAD(P)H oxidase activation.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-10206987,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-10329390,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-10455063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-10642331,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-10716919,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-11073878,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-11451740,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-11498076,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-11959628,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-11978735,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-12388315,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-12437086,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-14685281,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-15020207,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-15255178,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-15313955,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-15471985,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-15995169,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-16344372,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-16427865,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-16473958,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-16502253,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-17404153,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-18162606,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-3838314,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-9008168,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-9389480,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-9545226,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-9666719,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-9687493,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19345232-9811821
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1,2-Dihydroxybenzene-3,5-Disulfonic...,
http://linkedlifedata.com/resource/pubmed/chemical/Bradykinin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcimycin,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin L,
http://linkedlifedata.com/resource/pubmed/chemical/Cathepsins,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Endostatins,
http://linkedlifedata.com/resource/pubmed/chemical/Free Radical Scavengers,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1095-9319
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
78
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
45-50
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pubmed:dateRevised |
2010-12-28
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pubmed:meshHeading |
pubmed-meshheading:19345232-1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt,
pubmed-meshheading:19345232-Animals,
pubmed-meshheading:19345232-Bradykinin,
pubmed-meshheading:19345232-Calcimycin,
pubmed-meshheading:19345232-Cathepsin L,
pubmed-meshheading:19345232-Cathepsins,
pubmed-meshheading:19345232-Cattle,
pubmed-meshheading:19345232-Coronary Vessels,
pubmed-meshheading:19345232-Cysteine Endopeptidases,
pubmed-meshheading:19345232-Dose-Response Relationship, Drug,
pubmed-meshheading:19345232-Endostatins,
pubmed-meshheading:19345232-Endothelial Cells,
pubmed-meshheading:19345232-Endothelium, Vascular,
pubmed-meshheading:19345232-Enzyme Activation,
pubmed-meshheading:19345232-Free Radical Scavengers,
pubmed-meshheading:19345232-NADPH Oxidase
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pubmed:year |
2009
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pubmed:articleTitle |
Dependence of cathepsin L-induced coronary endothelial dysfunction upon activation of NAD(P)H oxidase.
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pubmed:affiliation |
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, 410 N 12th, Richmond, VA 23298, USA.
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pubmed:publicationType |
Journal Article
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