title: Elevated secretory non-pancreatic type II phospholipase A2 serum activity is associated with impaired endothelial vasodilator function in patients with coronary artery disease.
abstract: Low-grade inflammatory activity is associated with an increased risk for ischaemic coronary events. sPLA(2) (secretory non-pancreatic type II phospholipase A(2)) 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 sPLA(2) is associated with an impaired vasodilator function in patients with documented CAD (coronary artery disease). Endothelium-dependent (acetylcholine, 10-50 microg/min) and endothelium-independent (sodium nitroprusside, 2-8 microg/min) FBF (forearm blood flow) responses were measured by venous occlusion plethysmography in 50 male patients with angiographically documented CAD. sPLA(2) serum activity was inversely correlated with acetylcholine-induced FBF responses ( r =-0.36; P <0.05). In addition, there was a significant correlation between sPLA(2) and CRP (C-reactive protein; r =0.33, P <0.02). In contrast, FBF responses to sodium nitroprusside did not correlate with sPLA(2) 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 sPLA(2) ( 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 sPLA(2) serum activity is associated with a significant impairment in systemic endothelial vasodilator function in patients with CAD. The identification of sPLA(2) as a novel independent predictor for endothelial dysfunction provides another important clue to link a systemic marker of inflammation with coronary atherosclerotic disease.
authors.affiliation: Division of Cardiology, Department of Internal Medicine IV, Johann W. Goethe University, 60590 Frankfurt, Germany. fichtlscherer@em.uni-frankfurt.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Fichtlscherer
authors.forename: Marietta
authors.initials: M
authors.lastname: Kaszkin
authors.forename: Susanne
authors.initials: S
authors.lastname: Breuer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis; D003324:Coronary Artery Disease / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010741:Phospholipases A / Q000097:blood*; D054467:Phospholipases A2; D012039:Regional Blood Flow; D012307:Risk Factors; D014664:Vasodilation
chemical_list: D002097:C-Reactive Protein; D010741:Phospholipases A; D054467:Phospholipases A2