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

Study Questions:

Is vasostatin-2 protective against vascular disease?

Methods:

Effects of vasostatin-1 and vasostatin-2 on induced expression of adhesion molecules in human arterial endothelial cells were tested. Vasostatin-1 and -2 levels were also examined in coronary endarterectomy specimens, atherosclerotic aortas, internal mammary arteries, and non-atherosclerotic aortas, as well as in peripheral blood mononuclear cells (PBMCs) from severe coronary artery disease (CAD) patients and healthy volunteers. Serum levels of vasostatin-2 were analyzed in 968 consecutive patients undergoing coronary angiography.

Results:

Vasostatin-1 and -2 both inhibited tumour necrosis factor-alpha (TNFα), angiotensin II, and oxidized low-density lipoprotein (oxLDL)-induced expression of adhesion molecules; and attenuated TNFα-induced adhesion of U937 monocytes to endothelial cells. Vasostatin-2 levels were 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. Serum vasostatin-2 levels were lower in CAD patients than in controls (p < 0.001). Vasostatin-2 levels 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.

Conclusions:

The authors concluded that 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.

Perspective:

Chromogranin A (a protein co-released with catecholamines) is the precursor to several biologically active peptides generated by proteolytic cleavage, including vasostatins. Vasostatin-1 and -2 have been previously shown to exhibit anti-inflammatory properties with protective vascular effects. This study demonstrates that in addition to blocking the effect of multiple proinflammatory stimuli on endothelial cells in vitro, vasostatin-2 levels are inversely associated with atherosclerosis in humans. These results suggest that administration of vasostatin-2 could provide protection against vascular disease. However, further studies to establish a causal relationship between vasostatin-2 and atherosclerosis are needed.

Clinical Topics: Cardiac Surgery, Dyslipidemia, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Aortic Surgery, Cardiac Surgery and Heart Failure, Lipid Metabolism, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Endarterectomy, Coronary Artery Disease, Atherosclerosis, Atherectomy, Catecholamines, Vascular Diseases, Lipoproteins, Tumor Necrosis Factor-alpha, Heart Diseases, Biological Markers, Coronary Angiography, Heart Failure, Cell Adhesion Molecules, Endothelial Cells


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