Endothelial cell markers reflecting endothelial cell dysfunction in patients with mixed connective tissue disease.
BACKGROUND
The aim of the present study was to investigate the association between cardiovascular risk factors and endothelial dysfunction in patients with mixed connective tissue disease (MCTD) and to determine which biomarkers are associated with atherosclerotic complications, such as cardiovascular disease.


METHODS
Fifty MCTD patients and 38 healthy age-matched and sex-matched controls were enrolled in this study. In order to describe endothelial dysfunction, we assessed flow-mediated dilation (FMD), nitrate-mediated dilation (NMD) and carotid artery intima-media thickness (IMT). We investigated FMD of the brachial artery after reactive hyperemia and NMD after sublingual nitroglycerin administration, while the IMT of the common carotid artery was determined by ultrasound. Anti-U1 ribonucleoprotein (anti-U1RNP) antibodies, anti-cardiolipin (anti-CL) antibodies, anti-endothelial cell antibody (AECA) and endothelial cell markers, such as soluble thrombomodulin (TM) and von Willebrand factor antigen (vWFAg), were assessed.


RESULTS
The endothelium-dependent vasodilation (FMD) was significantly impaired in patients with MCTD, as compared with controls (%FMD: 4.7+/-4.2% vs. 8.7+/-5.0%; P<0.001), while the percentage NMD did not differ (%NMD: 14.3+/-6.6% vs. 17.1+/-6.7%; P=0.073). Mean carotid IMT values were higher in patients than in controls (IMT: MCTD, 0.64+/-0.13 mm vs. controls, 0.53+/-0.14 mm; P<0.001). FMD negatively correlated with disease duration, the levels of apolipoprotein A1, the paraoxonase-1 activity, and systolic blood pressure in MCTD patients. The percentage FMD was significantly lower in MCTD patients with cardiovascular diseases (CVD), than in those without CVD (%FMD: 3.5+/-2.9 vs. 5.8+/-4.8, P<0.0002), while percentage NMD did not differ between patients with and without CVDs. Serum levels of autoantibodies (anti-U1RNP, AECA and anti-CL) were significantly higher in MCTD patients and differed between MCTD patients with and without CVD. Endothelial cell markers such as soluble TM (12.2+/-8.1 ng/ml vs. 3.2+/-1.3 ng/ml; P<0.001) and vWFAg (224.1+/-115% vs. 89.4+/-27.1%, P<0.001) were the highest in MCTD patients with CVD.


CONCLUSIONS
FMD is a reliable sensitive marker of endothelial cell dysfunction in MCTD. Beside the traditional risk factors, anti-U1RNP, AECA and anti-CL antibodies may be important not only in the pathogenesis of MCTD but in the induction of endothelial cell activation, and may play crucial roles in the development of early atherosclerosis in MCTD.
Soltesz
Pal
P
3rd Department of Medicine, Medical and Health Science Center, University of Debrecen, Moricz Zs, Str, 22, Debrecen 4032, Hungary. soltesz@gmail.com
Bereczki
Daniel
D
Szodoray
Peter
P
Magyar
Maria T
MT
Der
Henrietta
H
Csipo
Istvan
I
Hajas
Agota
A
Paragh
Gyorgy
G
Szegedi
Gyula
G
Bodolay
Edit
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D050197:Atherosclerosis / Q000453:epidemiology; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D002308:Cardiolipins / Q000276:immunology; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D008947:Mixed Connective Tissue Disease / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D005996:Nitroglycerin / Q000494:pharmacology; D012261:Ribonucleoproteins / Q000276:immunology; D012307:Risk Factors; D012680:Sensitivity and Specificity; D018180:Thrombomodulin / Q000097:blood*; D017539:Tunica Intima / Q000000981:diagnostic imaging*; D017540:Tunica Media / Q000000981:diagnostic imaging*; D014463:Ultrasonography; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism*
D000906:Antibodies; D001323:Autoantibodies; D015415:Biomarkers; D002308:Cardiolipins; D012261:Ribonucleoproteins; D018180:Thrombomodulin; D014665:Vasodilator Agents; C087589:anti-endothelial cell antibody; D014841:von Willebrand Factor; D005996:Nitroglycerin
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