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(Circulation Research. 2001;89:298.)
© 2001 American Heart Association, Inc.

Review

Phospholipase A₂ in Vascular Disease

Eva Hurt-Camejo, Germán Camejo, Helena Peilot, Katarina Öörni, Petri Kovanen

From AstraZeneca R&D (E.H.-C., G.C.), Cell Biology and Biochemistry, Mölndal; Wallenberg Laboratory (E.H.-C., G.C., H.P.), Göteborg University, Sweden; and Wihuri Research Institute (K.O., P.K.), Helsinki, Finland.

Correspondence to Eva Hurt-Camejo, Cell Biology and Biochemistry, AstraZeneca, R&D, S-431 83, Mölndal, Sweden. E-mail Eva.Hurt-Camejo{at}astrazeneca.com

Secretory phospholipase A₂ (PLA₂) can be proatherogenic both in the circulation and in the arterial wall. In blood plasma, PLA₂ can modify the circulating lipoproteins and so induce formation of small dense LDL particles, which are associated with increased risk for cardiovascular disease. In the arterial wall, PLA₂ can hydrolyze lipoproteins. The PLA₂-modified lipoproteins bind tightly to extracellular proteoglycans, which may lead to their enhanced retention in the arterial wall. The modified lipoproteins may also aggregate and fuse, which can lead to accumulation of their lipids within the extracellular matrix. The PLA₂-modified particles are more susceptible to further modifications by other enzymes and agents and can be taken up by macrophages, leading to accumulation of intracellular lipids. In addition, lysophospholipids and free fatty acids, the hydrolysis products of PLA₂, promote atherogenesis. Thus, these lipid mediators can be carried, either by the PLA₂-modified lipoproteins themselves or by albumin, into the arterial cells, which then undergo functional alterations. This may, in turn, lead to specific changes in the extracellular matrix, which increase the retention and accumulation of lipoproteins within the matrix. In the present article, we discuss the possible actions of PLA₂ enzymes, especially PLA₂-IIA, in the arterial wall during atherogenesis.

Key Words: atherosclerosis • inflammation • cytokines • lipases • lysophospholipids

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