title: Plasma levels of vasostatin-1, a chromogranin A fragment, are associated with carotid artery maximum stenosis: A pilot study.
abstract: BACKGROUND
  Chromogranin A (CgA), a circulating protein released by the neuroendocrine system, can regulate vascular physiology and angiogenesis. Full-length CgA (CgA1-439) and its fragment CgA1-76(called vasostatin-1, VS-1) preserve the physiological integrity of the endothelial barrier function and are antiangiogenic, whereas CgA1-373is 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 CgA1-439, VS-1, CgA1-373, and total-CgA (CgA1-439plus 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Istituti Clinici Scientifici Maugeri, IRCCS Pavia, Clinical Trials Centre, Pavia, Italy. Electronic address: tiziana.bachetti@icsmaugeri.it.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Bachetti
authors.affiliation: Istituti Clinici Scientifici Maugeri, IRCCS Pavia and IRCCS Montescano, Angiology Unit, Pavia and Montescano, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ferrari Bardile
authors.affiliation: Istituti Clinici Scientifici Maugeri, IRCCS Pavia and IRCCS Montescano, Angiology Unit, Pavia and Montescano, Italy.
authors.forename: Teresa Lucia
authors.initials: TL
authors.lastname: Aloi
authors.affiliation: IRCCS San Raffaele Scientific Institute, Tumour Biology and Vascular Targeting Unit, Milan, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Colombo
authors.affiliation: IRCCS San Raffaele Scientific Institute, Tumour Biology and Vascular Targeting Unit, Milan, Italy.
authors.forename: Emma
authors.initials: E
authors.lastname: Assi
authors.affiliation: Istituti Clinici Scientifici Maugeri, IRCCS Pavia and IRCCS Montescano, Angiology Unit, Pavia and Montescano, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Savino
authors.affiliation: Istituti Clinici Scientifici Maugeri, IRCCS Pavia and IRCCS Montescano, Angiology Unit, Pavia and Montescano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Vercelli
authors.affiliation: Istituti Clinici Scientifici Maugeri, IRCCS Pavia, Bioengineering Service, Pavia, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Colombo
authors.affiliation: IRCCS San Raffaele Scientific Institute, Tumour Biology and Vascular Targeting Unit, Milan, Italy; San Raffaele Vita-Salute University, Milan, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Corti
mesh_terms: D015415:Biomarkers / Q000097:blood; D002340:Carotid Artery Diseases / Q000097:blood / Q000000981:diagnostic imaging; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging*; D016893:Carotid Stenosis / Q000097:blood* / Q000000981:diagnostic imaging*; D053379:Chromogranin A / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D010865:Pilot Projects; D018608:Ultrasonography, Doppler
chemical_list: D015415:Biomarkers; D053379:Chromogranin A; D010446:Peptide Fragments; C064110:vasostatin I
keywords: Atherosclerosis; Carotid artery; Chromogranin A; Doppler ultrasound; Vasostatin-1