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25-11-2010 | Cardiometabolic | Article

Inhibition of sPLA2 reduces atherogenic lipoproteins


Free abstract

MedWire News: A daily dose of the secretory phospholipase A2 (sPLA2) inhibitor varespladib methyl may be an effective anti-atherosclerotic treatment, a US study shows.

"Varespladib methyl treatment resulted in statistically significant dose-dependent reductions that were different from placebo in sPLA2 concentrations, low-density lipoprotein (LDL) cholesterol, and non-high-density lipoprotein (HDL) cholesterol," the researchers report.

Previous studies have shown that sPLA2 isoenzymes promote atherosclerosis by lipoprotein modification, retention, and oxidation.

In the Phospholipase Levels and Serological Markers of Atherosclerosis (PLASMA) phase II trial, Robert Rosenson (Mount Sinai School of Medicine, New York) and colleagues randomly allocated 135 stable coronary heart disease (CHD) patients to receive either varespladib methyl 250 mg, varespladib methyl 500 mg, or placebo, once daily for 8 weeks.

The team measured patients' sPLA2 concentrations, plasma lipids and lipoproteins, and inflammatory biomarkers at baseline and after the treatment period.

Overall, treatment with varespladib methyl significantly reduced sPLA2 concentration (78%), LDL cholesterol (8%), non-HDL cholesterol (10%), and apolipoprotein (apo)B (9%), compared with placebo.

More specifically, treatment with varespladib methyl 500 mg lowered sPLA2 concentration by 84%, LDL cholesterol by 15%, and apoB levels by 11%.

Relative to baseline levels, this treatment group also showed reduced LDL and small LDL particle concentrations (by 7% and 11% respectively).

"Through inhibition of sPLA2, it is possible that varespladib methyl may not only facilitate LDL clearance, but it may also reduce LDL retention in the vessel wall," the team explains.

In contrast, although varespladib methyl 250 mg lowered sPLA2 levels by 73%, the effects on lipids and lipoproteins were not significantly different from in the placebo group.

Writing in the European Heart Journal, Rosenson and team say: "From these results, we hypothesize that treatment with varespladib methyl 500 mg daily should be considered for further investigation as an anti-atherosclerotic agent in statin-treated patients."

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010

By Nikki Withers