Plasma levels of vasostatin-1, a chromogranin A fragment, are associated with carotid artery maximum stenosis: A pilot study

Background: Chromogranin A (CgA), a circulating protein released by the neuroendocrine system, can regulate vascular physiology and angiogenesis. Full-length CgA (CgA_1-439) and its fragment CgA_1-76 (called vasostatin-1, VS-1) preserve the physiological integrity of the endothelial barrier function and are antiangiogenic, whereas CgA_1-373 is proangiogenic. We investigated whether these polypeptides are altered in patients with various degrees of carotid artery atherosclerosis.

Methods: We studied 81 patients with carotid artery atherosclerosis, asymptomatic for cerebrovascular diseases. Carotid arteries were examined by Doppler ultrasound and plaque characteristics were recorded. Plasma levels of CgA_1-439, VS-1, CgA_1-373, and total-CgA (CgA_1-439 plus truncated fragments lacking part or the entire C-terminal region) were assessed by specific ELISAs.

Results: Plasma levels of VS-1 and total-CgA correlated with carotid artery maximum stenosis (r=0.349, p=0.001 and r=0.256, p=0.021, respectively). Stepwise multiple regression analysis indicated that VS-1 was a significant predictor of maximum stenosis after adjustment for age, gender, and conventional risk factors for atherosclerosis (regression coefficient=12.42, SE=4.84, p=0.012). In addition, logistic regression analysis indicated that relatively high levels of full-length CgA, but not total-CgA, predict the presence of hypoechoic, lipid-rich plaques (OR=1.47; 95% CI: 1.19-1.81, p=0.0003).

Conclusion: VS-1 is independently associated with carotid artery maximum stenosis. Furthermore, full-length CgA is an independent indicator of hypoechoic plaques, likely reflecting initial stages of atherosclerosis. Given the known capability of CgA and VS-1 to regulate vascular function and angiogenesis these polypeptides might play a role in the regulation of atherosclerosis pathophysiology.