Reduced serum levels of vasostatin-2, an anti-inflammatory peptide derived from chromogranin A, are associated with the presence and severity of coronary artery disease.
OBJECTIVE
We here investigated the endothelial effects of the chromogranin A-derived peptide vasostatin-2 and its relation to coronary artery disease (CAD).


RESULTS
We assessed the impact of recombinant vasostatin-1 and vasostatin-2 on tumour necrosis factor-alpha (TNFα)-, angiotensin II-, and oxidized low-density lipoprotein (oxLDL)-induced expression of adhesion molecules in human arterial endothelial cells. Vasostatin-1 and vasostatin-2 levels were examined in coronary endarterectomy specimens (n= 23), atherosclerotic aortas (n= 16), non-significant-atherosclerotic internal mammary arteries (n= 30), and non-atherosclerotic aortas (n= 10), as well as in peripheral blood mononuclear cells (PBMCs) from severe CAD patients (n= 50) and healthy volunteers (n= 21). Serum levels of vasostatin-2 were analysed in 968 consecutive patients undergoing coronary angiography. Vasostatin-1 and vasostatin-2 concentration-dependently inhibited TNFα-, angiotensin II-, and oxLDL-induced expression of adhesion molecules; and attenuated TNFα-induced adhesion of U937 monocytes to endothelial cells. Vasostatin-2 levels were significantly decreased in endarterectomy samples and atherosclerotic aortas compared with non-atherosclerotic internal mammary arteries and aortas, as well as in PBMCs of severe CAD patients compared with healthy controls (all P< 0.05). Serum vasostatin-2 levels were significantly lower in CAD patients (diameter stenosis ≥ 50%, n= 554) than in controls (normal arteries or diameter stenosis <30%, n= 281) (P< 0.001). Its concentrations correlated with the number of diseased coronary arteries and Syntax score in CAD patients (all P< 0.05). At multivariable regression analysis, decreased vasostatin-2 levels remained associated with CAD when other variables were taken into account.


CONCLUSIONS
Vasostatin-2 has anti-inflammatory properties and is decreased in atherosclerotic plaque specimens and in PBMC of CAD patients. Decreased serum vasostatin-2 levels are associated with the presence and severity of CAD.
Department of Cardiology,  Rui Jin Hospital, Shanghai Jiaotong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025,  People's Republic of China.
Lin
L
Lu
Ya Nan
YN
Wang
Ming Chun
MC
Li
Hai Bo
HB
Wang
Li Jin
LJ
Pu
Wen Quan
WQ
Niu
Hua
H
Meng
Er Li
EL
Yang
Rui Yan
RY
Zhang
Qi
Q
Zhang
Qiang
Q
Zhao
Qiu Jing
QJ
Chen
Raffaele
R
De Caterina
Wei Feng
WF
Shen
D000704:Analysis of Variance; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D053379:Chromogranin A / Q000172:deficiency* / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000097:blood / Q000209:etiology*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000172:deficiency* / Q000494:pharmacology; D011379:Prognosis; D011994:Recombinant Proteins / Q000494:pharmacology; D012044:Regression Analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D053379:Chromogranin A; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C064110:vasostatin I; C102106:vasostatin II; D002097:C-Reactive Protein