Association of serum antibodies to heat-shock protein 65 with carotid atherosclerosis

150-kD oxygen-regulated protein is expressed in human atherosclerotic plaques and allows mononuclear phagocytes to withstand cellular stress on exposure to hypoxia and modified low density lipoprotein.

“…During the course of lesion formation, certain cells that express ORP150 die (such as degenerating macrophages, observed in atherosclerotic lesions) or catastrophic events such as plaque rupture (41) disrupt a large number of cells, releasing their contents and allowing the host to mount an antibody response. Consistent with these data, autoantibody to other stress proteins has been detected in patient plasma (42). This may account for the other bands visualized when patient sera were reacted with lysates of hypoxic, vs lack of reactivity with normoxic, extracts of mononuclear phagocytes (Fig.…”

The effects of total lymphocyte deficiency on the extent of atherosclerosis in apolipoprotein E-/- mice.

“…There has been considerable interest in the role of autoantibodies and immune complexes in the development of atherosclerosis (15,16,17). The two antigens that have received the most attention are modified forms of lipoproteins and heat shock proteins.…”

“…Heat-shock protein 60 is one candidate antigen (15), although most attention has focused on autoantibodies to modified low density lipoprotein (LDL). Serum titers of antimalondialdehyde (MDA) 1 -LDL antibodies have been correlated with extent of atherosclerotic disease in humans (16).…”

Autoantibodies against heat shock protein 60 mediate endothelial cytotoxicity.

“…20 samples of human sera, divided into two groups, were selected according their anti-hsp serum antibody titers and the occurrence of atherosclerotic lesions in carotid arteries from 867 subjects investigated in a previous study (reference 8, Table I). The methods for determination of carotid atherosclerotic lesions and serum antibodies have been described elsewhere (8 (Sigma), the blots were probed with the affinity-purified human anti-hsp65/60 antibodies (50 ng/ml PBS supplemented with 1% BSA) or human high titer serum (diluted 1:500 vol/vol) for 5 h. The reaction was visualized using horseradish peroxidase-conjugated rabbit antihuman Ig secondary antibodies (Z259; Dakopatts), diluted 1:400 followed by addition of 4-chloro-1-naphthol/hydrogen peroxide (Sigma).…”

“…A previous epidemiological study (8) from our laboratory had demonstrated that serum antibodies to mycobacterial hsp65, which is a homologue of human hsp6O, were significantly increased in clinically healthy subjects with sonographically demonstrable carotid atherosclerosis compared to those without lesions. This increased antibody level was independent of other established risk factors, such as hyperlipidemia, smoking, hypertension, diabetes mellitus, and obesity, thus providing evidence for a strong correlation of hsp65 antibodies with carotid atherosclerosis.…”