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Endothelial nitric oxide synthase is essential for the HMG‐CoA reductase inhibitor cerivastatin to promote collateral growth in response to ischemia
Author(s) -
Sata Masataka,
Nishimatsu Hiroaki,
Suzuki Etsu,
Sugiura Seiryo,
Yoshizumi Masao,
Ouchi Yasuyoshi,
Hirata Yasunobu,
Nagai Ryozo
Publication year - 2001
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/fj.01-0415fje
Subject(s) - cerivastatin , enos , atorvastatin , pharmacology , nitric oxide synthase , chemistry , statin , nitric oxide , hmg coa reductase , ischemia , reductase , medicine , endocrinology , biochemistry , enzyme
HMG‐CoA (3‐hydroxy‐3‐methylglutaryl‐coenzyme A) reductase inhibitors, or statins, are prescribed widely to lower cholesterol. Accumulating evidence indicates that statins have various effects on vascular cells, which are independent of their lipid‐lowering effect. Here, we tested the hypothesis that statins may augment collateral flow to ischemic tissues. We induced hind‐limb ischemia in wild‐type mice and treated them with either saline or cerivastatin. Cerivastatin enhanced the blood flow recovery dramatically as determined by Laser Doppler imaging. The mice treated with saline displayed frequent autoamputation of the ischemic toe, which was prevented completely by cerivastatin. Anti‐CD31 immunostaining revealed that cerivastatin significantly increased the capillary density. Endothelial nitric oxide synthase (eNOS) activity was enhanced markedly in the mice treated with cerivastatin. The angiogenic effect of cerivastatin was abrogated in eNOS deficient (eNOS‐/‐) mice. These results indicate that eNOS is essential for cerivastatin to promote collateral growth in response to ischemia.