Expression of phospholipase A2 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. Phospholipase A2 (PLA2) has been shown to modify LDL particles in vitro by degrading its phospholipids, resulting in enhanced uptake by macrophages. Reaction products of PLA2 are lysophospholipids and nonesterified fatty acids (mainly arachidonic acid), which are precursors of potent inflammatory mediators and which have been found in atherosclerotic regions of the arterial wall. To elucidate the expression of PLA2 in normal and diseased arteries, frozen tissue sections of human nonatherosclerotic mesenteric artery and carotid plaques were examined by immunohistochemistry using specific antibodies against secretory PLA2 types I and II and cytosolic PLA2 (85 kd). Secretory PLA2 type I was not detected. High expression of secretory PLA2 type II was found throughout the media in both normal and atherosclerotic artery specimens, in which smooth muscle cells dominated. Cytosolic PLA2 was found exclusively in diseased artery, mainly in the intima in regions with an inflammatory infiltrate consisting of macrophages and smooth muscle cells. Furthermore, both normal and atherosclerotic artery possessed substantial PLA2 activity. It is suggested that secretory PLA2 type II could play an important role in early atherogenesis because it is present in the preatherosclerotic arterial wall, where it may lead to LDL modification, foam cell formation, and activation of immune mechanisms.
Elinder
L S
LS
Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Dumitrescu
A
A
Larsson
P
P
Hedin
U
U
Frostegård
J
J
Claesson
H E
HE
D001158:Arteries / Q000201:enzymology*; D001161:Arteriosclerosis / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2
D007527:Isoenzymes; D010741:Phospholipases A; D054467:Phospholipases A2