Temporal Expression of Heat Shock Proteins 60 and 70 at Lesion-Prone Sites During Atherogenesis in ApoE-Deficient Mice

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 21; no. 12; pp. 1991 - 1997
• Main Authors: Kanwar, Rupinder K, Kanwar, Jagat R, Wang, Dongmao, Ormrod, Douglas J, Krissansen, Geoffrey W
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.12.2001; Hagerstown, MD Lippincott
• Subjects: Animals; Aorta - metabolism; Aorta - pathology; Apolipoproteins E - deficiency; Arteries - metabolism; Arteries - pathology; Arteriosclerosis - metabolism; Arteriosclerosis - pathology; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blotting, Western; Cardiology. Vascular system; Chaperonin 60 - metabolism; Disease Models, Animal; Disease Progression; Down-Regulation; HSP70 Heat-Shock Proteins - metabolism; Immunohistochemistry; Macrophages - metabolism; Medical sciences; Mice; Mice, Mutant Strains; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; T-Lymphocytes - metabolism; Up-Regulation; Pathophysiology; Pathogenesis; Deficiency; Rodentia; Cardiovascular disease; Exploration; Gene expression; Genetic disease; Vascular disease; Vertebrata; Mammalia; Mouse; Apolipoprotein E; Animal; Atherosclerosis; Heat shock protein; Aorta; Evolution
• ISSN: 1079-5642; 1524-4636
• DOI: 10.1161/hq1201.100263

In the study, we investigate whether the expressions of heat shock protein (hsp)60 (a potential autoantigen) and the stress-inducible form of cytoprotector hsp70 are correlated with the development of atherosclerotic lesions in the aortic tree of apolipoprotein E–deficient (apoE) mice. The apoE mouse model is advantageous because the stress-inducible form of hsp70 is not constitutively expressed in mice, unlike primates; hence, tissues under stress can be clearly defined. Both mammalian hsps were detected newly expressed (before mononuclear cell infiltration) on aortic valves and endothelia at lesion-prone sites of 3-week-old apoE mice. In 8- and 20-week-old mice, they were strongly and heterogeneously expressed in early to advanced fibrofatty plaques, with levels correlating with lesion severity. Expression was markedly downregulated in advanced collagenous, acellular, calcified plaques of 40- and 69-week-old mice and was absent in control aortas of normocholesterolemic wild-type (apoE) mice. Western blot analysis of tissue homogenates confirmed the temporal expression of the hsps. Double immunostaining revealed that both hsps were expressed by lesional endothelial cells, macrophages, smooth muscle cells, and CD3 T lymphocytes. This study provides evidence that hsp60 and hsp70 are temporally expressed on all major cell types in lesion-prone sites during atherogenesis, suggesting that few cells escape the toxic environment of the atherosclerotic plaque.