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, Atherosclerotic Disease (CAD/PAD), 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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