Visceral adipose tissue accumulation, secretory phospholipase A2-IIA and atherogenecity of LDL

Abstract

Objective: The aim of the present study was to investigate the combined impact of visceral adipose tissue (VAT) and secretory group IIA phospholipase A 2 (sPLA 2 -IIA) concentrations on the atherogenicity of low-density lipoprotein (LDL) particles among men. Subjects: Analyses were conducted in 74 mid-obese healthy men (age: (mean7s.d.) 37.9711.7 years). Methods: Plasma levels of sPLA 2 -IIA were measured with a commercial ELISA and VAT levels were assessed by computed tomography. Distinct subpopulations of LDL particles were characterized from whole plasma using nondenaturating 2-16% gradient gel electrophoresis. Results: Data indicated that plasma sPLA 2 -IIA levels were approximately 29% (P ¼ 0.007) higher among men characterized by a higher accumulation of VAT (4142 vs p142 cm 2 ). Men having high plasma sPLA 2 -IIA levels (X127.2 ng/dl, the median value), were characterized by higher levels of plasma cholesterol (C) and apolipoprotein (apo) B, LDL-C, LDL-apoB, oxidized LDL (OxLDL) and by smaller LDL particles compared to men with sPLA 2 -IIAo127.2 ng/dl. Multiple regression analyses showed that plasma triglycerides and sPLA 2 -IIA levels explained 22.7 and 11.8% of the variance in LDL peak particle size, respectively. Levels of VAT and of sPLA 2 -IIA were the strongest correlates of OxLDL levels explaining, respectively, 15.0 and 5.5% of their variability. Conclusion: Both VAT and sPLA 2 -IIA levels modulate the atherogenecity of LDL by accounting for the reduction in their size and their susceptibility to oxidation.

A Representative GIIA Phospholipase A2 Activates Preadipocytes to Produce Inflammatory Mediators Implicated in Obesity Development

“…Levels of sPLA 2 are elevated in the serum of obese patients as well as in inflamed fat tissue [1,2,50,51]. Previous studies have implicated sPLA 2 s in metabolic diseases, including obesity [1,4,6].…”

Relationship of visceral and subcutaneous adipose depots to markers of arterial injury and inflammation among individuals with HIV

“…Moreover, application of a LpPLA2 inhibitor also reduced oxLDL production from human adipocytes [22]. Excess VAT has been correlated with oxLDL among PLWOH [23]. In contrast, few data are available on these markers of arterial disease in relation to body composition among PLWH.…”

Inhibition of Secretory Phospholipase A2 in Patients with Acute Coronary Syndromes: Rationale and Design of the Vascular Inflammation Suppression to Treat Acute Coronary Syndrome for 16 Weeks (VISTA-16) Trial

“…The action of sPLA 2 on LDL results in smaller particles that are more susceptible to oxidative modification and to uptake by macrophages, the seminal events in foam cell formation [17]. Indeed, clinical data associate increasing levels of sPLA 2 with higher levels of oxidized LDL and smaller circulating LDL particles [18]. Moreover, the hydrolysis of lipoprotein phospholipid by sPLA 2 generates free fatty acids and lysophospholipid products that may independently promote inflammation and oxidative stress within the arterial wall [16,19].…”