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Immunologic Research

, Volume 60, Issue 1, pp 50–59 | Cite as

Increased levels of anti-heat-shock protein 60 (anti-Hsp60) indicate endothelial dysfunction, atherosclerosis and cardiovascular diseases in patients with mixed connective tissue disease

  • Edit Bodolay
  • Zoltan Prohászka
  • Gyorgy Paragh
  • Istvan Csipő
  • Gabor Nagy
  • Renata Laczik
  • Nora Demeter
  • Eva Zöld
  • Britt Nakken
  • Gyula Szegedi
  • Peter SzodorayEmail author
Article

Abstract

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.

Keywords

Mixed connective tissue disease Anti-Hsp60 antibody Dyslipidemia Endothelial dysfunction Atherosclerosis Cardiovascular disease 

Abbreviations

AECA

Anti-endothelial cell antibodies

ANA

Antinuclear antibodies

Apo(A1,B)

Apolipoprotein

β2GPI

β2-Glycoprotein I

BMI

Body mass index

BP

Blood pressure

CL

Cardiolipin

CS

Corticosteroid

CVD

Cardiovascular disease

dsDNA

Double-stranded deoxyribonucleic acid

ECG

Electrocardiography

ELISA

Enzyme-linked immunosorbent assay

EMG

Electromyography

ENG

Electroneurography

ET-1

Endothelin-1

GN

Glomerulonephritis

HDL

High-density lipoprotein

hsCRP

High-sensitivity C-reactive protein

Hsp

Heat-shock protein

HRCT

High-resolution CT scanning

IMT

Carotid artery intima–media thickness

LDL

Low-density lipoprotein

MCTD

Mixed connective tissue disease

NSAID

Nonsteroidal anti-inflammatory drugs

oxLDL

Oxidized low-density lipoprotein

PAH

Pulmonary arterial hypertension

PON

Paraoxonase activity

U1-RNP

Uridine-rich ribonucleoprotein

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Edit Bodolay
    • 1
  • Zoltan Prohászka
    • 2
  • Gyorgy Paragh
    • 3
  • Istvan Csipő
    • 1
  • Gabor Nagy
    • 1
  • Renata Laczik
    • 4
  • Nora Demeter
    • 5
  • Eva Zöld
    • 1
  • Britt Nakken
    • 6
  • Gyula Szegedi
    • 1
  • Peter Szodoray
    • 6
    Email author
  1. 1.Department of Clinical Immunology, Institute of MedicineUniversity of Debrecen Medical and Health Science CenterDebrecenHungary
  2. 2.Research Laboratory, 3rd Department of Internal MedicineSemmelweis UniversityBudapestHungary
  3. 3.Division of Metabolic Diseases, Institute of MedicineUniversity of Debrecen Medical and Health Science CenterDebrecenHungary
  4. 4.Institute of ImmunologyUniversity of Debrecen Medical and Health Science CenterDebrecenHungary
  5. 5.Department of Radiology, Medical SchoolUniversity of PécsPecsHungary
  6. 6.Institute of Immunology, Rikshospitalet, Oslo University HospitalUniversity of OsloOsloNorway

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