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 (P en), clusterin, and apolipoprotein (ape) A-I accumulate in the artery wall during the development of atherosclerosis. In normal aortas (n=6) there were low levels of extracellular Pen, clusterin, and apoA-I imm unoreactivity. The cytoplasm of smooth muscle cells in the media showe d granular positivity for both Pon and apoA-I, indicating that these p roteins were undergoing lysosomal degradation. This activity was also indicated by the presence of both intact and degradation products of P on in smooth muscle cells as shown by Western blotting. With the progr ession of disease from fatty streaks (n=3) to advanced atherosclerosis (n=8) there was an increase in Pen, apoA-I, and clusterin immunoreact ivity, indicating the increasing presence of these proteins with disea se progression. These proteins are the components of a specific HDL su bspecies that has been implicated in the prevention of peroxidative da mage to phospholipids in LDL and membranes. The increase in Pen, clust erin, and apoA-I during the development of atherosclerosis may therefo re represent a protective response to the oxidative stress associated with the development of atherosclerosis.