EXPRESSION OF PHOSPHOLIPASE A(2) ISOFORMS IN HUMAN NORMAL AND ATHEROSCLEROTIC ARTERIAL-WALL

LDL particles must be modified in the arterial wall to be taken up by macrophages at an excessive rate, leading to foam cell formation. Phos pholipase A(2) (PLA(2)) has been shown to modify LDL particles in vitr o by degrading its phospholipids, resulting in enhanced uptake by macr ophages. Reaction products of PLA(2) are lysophospholipids and noneste rified fatty acids (mainly arachidonic acid), which are precursors of potent inflammatory mediators and which have been found in atheroscler otic regions of the arterial wall. To elucidate the expression of PLA( 2) in normal and diseased arteries, frozen tissue sections of human no natherosclerotic mesenteric artery and carotid plaques were examined b y immunohistochemistry using specific antibodies against secretory PLA (2) types I and II and cytosolic PLA(2) (85 kd). Secretory PLA(2) type I was not detected. High expression of secretory PLA(2) type II was f ound throughout the media in both normal and atherosclerotic artery sp ecimens, in which smooth muscle cells dominated. Cytosolic PLA(2) was found exclusively in diseased artery, mainly in the intima in regions with an inflammatory infiltrate consisting of macrophages and smooth m uscle cells. Furthermore, both normal and atherosclerotic artery posse ssed substantial PLA(2) activity. It is suggested that secretory PLA(2 ) type II could play an important role in early atherogenesis because it is present in the preatherosclerotic arterial wan, where it may lea d to LDL modification, foam cell formation, and activation of immune m echanisms.