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

Abstract

We here investigated the endothelial effects of the chromogranin A-derived peptide vasostatin-2 and its relation to coronary artery disease (CAD). 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. 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.