Distribution and Synthesis of Apolipoprotein J in the Atherosclerotic Aorta

Abstract

Abstract-The distribution of apolipoprotein (apo) J during the development of atherosclerosis in the human aorta was evaluated by immununohistochemical observation, together with the other apolipoprotein A-I, A-II, B, C-III, and E. Although apoJ was never observed in the normal aorta (ie, without any intimal lesions or intimal thickening), it was distributed not only in the intima but also in the media of aortas with diffuse, intimal thickening or atherosclerotic lesions. Double immunostaining with antibodies for apoJ and ␣-smooth muscle actin revealed apoJ deposition in smooth muscle cells (SMCs) or the aortic stroma in the vicinity of SMCs. The extent of apoJ distribution in the aortic wall increased with the degree of atherosclerosis development. In addition, the distribution pattern of apoJ was very similar to that of apoA-I and E. In situ hybridization with human apoJ cDNA demonstrated intense signals in cells scattered within the subendothelial space and medial SMCs of the aorta with advanced atherosclerosis but not in those of the normal aorta without intimal thickening. Furthermore, reverse transcriptase-polymerase chain reaction of the cultured human aortic SMCs revealed apoJ mRNA expression in these cells. The results indicate that apoJ in the aortic wall originates from not only apoJ circulated in the plasma but also apoJ produced by SMCs in the aortic wall. Considering the similarities of the distribution between apoJ and apo-A-I or E, we hypothesize that apoJ possibly has a protective role against human atherosclerosis by its involvement with cholesterol transport from the aortic wall to the liver.

Apolipoprotein J/Clusterin Is Induced in Vascular Smooth Muscle Cells After Vascular Injury

“…The reason for this discrepancy is thought to be that apoJ accumulated in the media and neointima of aorta at 24 weeks, because apoJ is distributed in the intima and media of human aortas with intimal thickening or atherosclerotic lesion. 20 Several investigators have reported that apoJ is induced after tissue injury or inflammation in a variety of tissues. Swertfeger et al 21 reported that apoJ protein accumulates in myocytes at the interface between degenerated myocardial tissue and the surrounding cardiac tissue in myosin-induced and viral myocarditis.…”

Thematic review series: The Immune System and Atherogenesis. Lipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease?

“…Although little is known about its precise function, its presence in atherosclerotic lesions but not in normal arteries (180) suggests a role in the atherosclerosis associated with chronic inflammatory states. Its colocalization in lesions with apoA-I and apoE (180) suggests that it may enter lesions in association with HDL particles, which can be retained by vascular proteoglycans if they contain positively charged apolipoproteins such as apoE (181,182) or SAA (102). Like SAA, apoJ can be synthesized by vascular cells, especially arterial smooth muscle cells and foam cells (180).…”

“…Its colocalization in lesions with apoA-I and apoE (180) suggests that it may enter lesions in association with HDL particles, which can be retained by vascular proteoglycans if they contain positively charged apolipoproteins such as apoE (181,182) or SAA (102). Like SAA, apoJ can be synthesized by vascular cells, especially arterial smooth muscle cells and foam cells (180). It also is released during the platelet aggregation (183) that occurs during thrombosis and plaque rupture.…”

Serum Apolipoprotein J in Health, Coronary Heart Disease and Type 2 Diabetes Mellitus

“…The same particles also contain apo A-and paraoxonase (PON1) 5,7) . Apo J is present in human and mouse atherosclerotic lesions, but not in normal arterial tissue 10,11) . In tissue culture, it acts as an acceptor of cholesterol from macrophage-derived foam cells 3) .…”