Increased levels of anti-heat-shock protein 60 (anti-Hsp60) indicate endothelial dysfunction, atherosclerosis and cardiovascular diseases in patients with mixed connective tissue disease.
Heat-shock protein 60 (Hsp60) has been shown to provoke inflammation, and anti-Hsp60 may facilitate the development of atherosclerosis. In this study, we have investigated 30 patients with mixed connective tissue disease (MCTD) and assessed anti-Hsp60 and their relationship to cardiovascular diseases (CVD). Out of 30 patients with MCTD, 15 had CVDs. Anti-Hsp60 antibody was determined by enzyme-linked immunosorbent assay. Since endothelial dysfunction and accelerated atherosclerosis are characteristic to MCTD, a wide array of MCTD-, endothelial dysfunction- and CVD-associated parameters was investigated: serum lipid levels, paraoxonase activity (PON1), rich nuclear ribonucleoprotein U1 (anti-U1RNP), anti-endothelial cell antibodies, anti-cardiolipin and anti-β2-glycoprotein I antibody isotypes (anti-CL and anti-β2GPI), endothelin-1 (ET-1) levels, also intima-media thickness (IMT), a quantitative indicator of atherosclerosis. In MCTD, anti-Hsp60 antibody levels were significantly higher than in healthy individuals (p < 0.02). MCTD patients with CVD had significantly higher levels of anti-Hsp60 compared to MCTD without CVD (p = 0.001). Patients with MCTD had significantly lower high-density lipoprotein cholesterol (p = 0.02) and PON activity (p < 0.001), and significantly increased systolic (p < 0.0002) and diastolic (p < 0.001) blood pressure compared to healthy individuals. Anti-U1RNP levels (p < 0.002) and IMT were higher in patients compared to controls (p = 0.002). The CVD-positive MCTD patients had increased anti-Hsp60 (p < 0.0013), anti-CL IgG (p = 0.0005), ET-1 serum concentration (p < 0.05) and IMT levels (p < 0.001) compared to MCTD patients without CVD. Anti-Hsp60 showed a strong correlation with anti-oxLDL (r = 0.36, p = 0.01) and serum ET-1 (r = 0.62, p < 0.001) and negative correlation with PON activity (r = -0.47, p = 0.01). Anti-Hsp60 indicates endothelial injury, CVD, and can function as a novel atherosclerotic risk factor, also a valuable diagnostic marker in patients with MCTD.
Department of Clinical Immunology, Institute of Medicine, University of Debrecen Medical and Health Science Center, Debrecen, Hungary.
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E
Bodolay
Zoltan
Z
Prohászka
Gyorgy
G
Paragh
Istvan
I
Csipő
Gabor
G
Nagy
Renata
R
Laczik
Nora
N
Demeter
Eva
E
Zöld
Britt
B
Nakken
Gyula
G
Szegedi
Peter
P
Szodoray
D000328:Adult; D000368:Aged; D043303:Aryldialkylphosphatase / Q000097:blood; D001323:Autoantibodies / Q000276:immunology*; D002308:Cardiolipins / Q000276:immunology; D002318:Cardiovascular Diseases / Q000276:immunology*; D018834:Chaperonin 60 / Q000276:immunology*; D019332:Endothelin-1 / Q000097:blood; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008055:Lipids / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000276:immunology*
D001323:Autoantibodies; D002308:Cardiolipins; D018834:Chaperonin 60; D019332:Endothelin-1; D007074:Immunoglobulin G; D008055:Lipids; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human