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(Circulation Research. 2000;86:610.)
© 2000 American Heart Association, Inc.

Editorials

Secretory Group II Phospholipase A₂

A Newly Recognized Acute-Phase Reactant With a Role in Atherogenesis

Petri T. Kovanen, Markku O. Pentikäinen

From the Wihuri Research Institute, Helsinki, Finland.

Correspondence to Petri T. Kovanen, MD, PhD, Wihuri Research Institute, Kalliolinnantie 4, FIN-00140 Helsinki, Finland. E-mail petri.kovanen@wri.fi

Key Words: atherosclerosis • extracellular matrix • phospholipase A₂ • proteoglycans

	Introduction

 
There is compelling evidence that atherosclerosis is an inflammatory disease.¹ Increased levels of markers of systemic inflammation, such as the acute-phase reactant C-reactive protein, have been associated with acute coronary events in patients with atherosclerosis.² The secretory group II phospholipase A₂ (sPLA₂) recently has been added to the group of acute-phase reactants,³ and its plasma levels are greatly increased in diseases involving systemic inflammation, such as sepsis and rheumatoid arthritis.⁴ Thus, hepatocytes synthesize and secrete this enzyme in response to inflammatory cytokines such as interleukin-6, tumor necrosis factor-, and interleukin-1.³ Plasma levels of sPLA₂ were found to correlate with levels of C-reactive protein in patients with atherosclerosis, and the levels of sPLA₂ were found to be good predictors of coronary events.⁵ Whether sPLA₂ is causally involved in the pathogenesis of atherosclerosis has been under investigation during recent years.

PLA₂s are enzymes that hydrolyze the acyl group at the sn-2 position of phospholipids. This results in the formation of a free fatty acid and a lysophospholipid that can be further metabolized into lipid mediators, including eicosanoids, platelet-activating factors, and lysophosphatidic acid.⁴ Mammalian PLA₂s are present in both cytosolic and secreted forms. The secretory PLA₂s consist of the group I enzyme secreted by the pancreas and the group II enzymes secreted by many cell types in a number of tissues. Group II sPLA₂ is a 14-kDa enzyme, which contains 7 disulfide bridges that make it very stable. It is highly cationic, which allows electrostatic interaction between . . . [Full Text of this Article]

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