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Free Fatty Acids Impair Release of Endothelial Nitric Oxide Via Activation of μ‐Calpain
Author(s) -
Scalia Rosario,
Berzins Brett
Publication year - 2007
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.21.6.a829-a
Subject(s) - calpain , nitric oxide , endothelium , chemistry , endothelial dysfunction , inflammation , medicine , nitric oxide synthase type iii , endocrinology , nitric oxide synthase , biochemistry , enos , biology , enzyme
Free Fatty Acids (FFA) induce endothelial dysfunction and vascular inflammation. We have previously reported that μ‐calpain activity causes loss of endothelial nitric oxide and increased leukocyte trafficking in the microcirculation. We report now evidence that links the inflammatory action of FFA to μ‐calpain activity. We measured μ‐calpain activity and release of endothelial Nitric Oxide in macro‐ and micro‐vascular endothelia exposed to 1‐μM‐ 1‐mM linoleic acid or palmitic acid. FFA significantly increased calpain activity and impaired release of endothelia nitric oxide (p<0.01 versus vehicle). These effects of FFA were blocked by pretreatment of endothelial cells with the selective calpain inhibitor ZLLal (10 μM, 3 hrs before study). Western blot analyses of the ubiquitously expressed μ‐ and m‐calpain isoforms in the isolated vascular endothelium, demonstrated increased μ‐calpain activity in response to FFA. Our data provide evidence for a new signaling pathway implicated in the endothelial damaging action of FFA.