Low-grade inflammatory activity is associated with an increased risk for ischaemic coronary events. sPLA2 (secretory non-pancreatic type II phospholipase A2) serum activity is increased in chronic inflammatory diseases and may also contribute to atherogenesis. Since the endothelium is a major target for inflammatory cytokines, we hypothesized that elevated serum activity of sPLA2 is associated with an impaired vasodilator function in patients with documented CAD (coronary artery disease). Endothelium-dependent (acetylcholine, 10–50 µg/min) and endothelium-independent (sodium nitroprusside, 2–8 µg/min) FBF (forearm blood flow) responses were measured by venous occlusion plethysmography in 50 male patients with angiographically documented CAD. sPLA2 serum activity was inversely correlated with acetylcholine-induced FBF responses (r=-0.36; P<0.05). In addition, there was a significant correlation between sPLA2 and CRP (C-reactive protein; r=0.33, P<0.02). In contrast, FBF responses to sodium nitroprusside did not correlate with sPLA2 serum activity. In order to identify independent predictors of an impaired endothelium-dependent vasodilator function in patients with CAD, a multivariate analysis was performed including the inflammatory serum markers as well as classical risk factors of CAD. This analysis demonstrated that both sPLA2 (P<0.05) and CRP serum levels (P<0.05) were the only significant independent predictors of an impaired acetylcholine-induced FBF response. In conclusion, elevated sPLA2 serum activity is associated with a significant impairment in systemic endothelial vasodilator function in patients with CAD. The identification of sPLA2 as a novel independent predictor for endothelial dysfunction provides another important clue to link a systemic marker of inflammation with coronary atherosclerotic disease.
Elevated secretory non-pancreatic type II phospholipase A2 serum activity is associated with impaired endothelial vasodilator function in patients with coronary artery disease
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Stephan FICHTLSCHERER, Marietta KASZKIN, Susanne BREUER, Stefanie DIMMELER, Andreas M. ZEIHER; Elevated secretory non-pancreatic type II phospholipase A2 serum activity is associated with impaired endothelial vasodilator function in patients with coronary artery disease. Clin Sci (Lond) 1 May 2004; 106 (5): 511–517. doi: https://doi.org/10.1042/CS20030399
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