Increased immunolocalization of paraoxonase, clusterin, and apolipoprotein A-I in the human artery wall with the progression of atherosclerosis.
Using immunolocalization techniques, we have shown that paraoxonase (Pon), clusterin, and apolipoprotein (apo) A-I accumulate in the artery wall during the development of atherosclerosis. In normal aortas (n = 6) there were low levels of extracellular Pon, clusterin, and apoA-I, immunoreactivity. The cytoplasm of smooth muscle cells in the media showed granular positivity for both Pon and apoA-I, indicating that these proteins were undergoing lysosomal degradation. This activity was also indicated by the presence of both intact and degradation products of Pon in smooth muscle cells as shown by Western blotting. With the progression of disease from fatty streaks (n = 3) to advanced atherosclerosis (n = 8) there was an increase in Pon, apoA-I, and clusterin immunoreactivity, indicating the increasing presence of these proteins with disease progression. These proteins are the components of a specific HDL subspecies that has been implicated in the prevention of peroxidative damage to phospholipids in LDL and membranes. The increase in Pon, clusterin, and apoA-I during the development of atherosclerosis may therefore represent a protective response to the oxidative stress associated with the development of atherosclerosis.
Mackness
B
B
Department of Medicine, University of Manchester, Royal Infirmary, UK.
Hunt
R
R
Durrington
P N
PN
Mackness
M I
MI
D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000378:metabolism*; D001055:Apolipoproteins B / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism*; D043303:Aryldialkylphosphatase; D015153:Blotting, Western; D002648:Child; D051152:Clusterin; D004730:Endothelium, Vascular / Q000201:enzymology; D004950:Esterases / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008075:Lipoproteins, HDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D009131:Muscle, Smooth, Vascular / Q000201:enzymology
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; C495242:CLU protein, human; D051152:Clusterin; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D018832:Molecular Chaperones; D004950:Esterases; D043303:Aryldialkylphosphatase