title: Circulating endothelial microparticles are elevated in bicuspid aortic valve disease and related to aortic dilation.
abstract: OBJECTIVE
  The mechanisms underlying aortic dilation in bicuspid aortic valve (BAV) disease are unknown. Circulating endothelial microparticles (EMPs) have emerged as biomarkers of endothelial damage. We sought to evaluate the relationships among EMPs, BAV disease, and aortic dilation.
  
  
  METHODS
  Four evaluations were used. Circulating EMPs (PECAM(+), E-selectin(+)) were compared between BAV patients and tricuspid aortic valve (TAV) control subjects. The variables related to circulating EMPs were investigated in BAV patients. Circulating EMP levels were compared between BAV and TAV patients with a dilated aorta. Finally, circulating EMPs in BAV patients were evaluated over time with respect to aortic valve surgery (AVS) or aortic surgery.
  
  
  RESULTS
  We observed higher levels of circulating PECAM(+) EMPs in the BAV patients than in the control subjects (3.98±0.2 vs. 2.39±0.4 per log PECAM(+) EMPs/μl, p=0.001). Aortic dilation was the most significant variable that correlated with the PECAM(+) EMP levels in the BAV patients (β=0.321, p=0.008). The BAV patients with aortic dilation exhibited higher PECAM(+)EMP levels than the TAV patients with dilated aortas, and this correlation was independent of aortic valve function. We observed a drastic decrease in the circulating PECAM(+) EMPs following AVS and aortic root replacement (4.27±0.6 and 1.75±0.3 per log PECAM(+)EMPs/μl, p=0.002).
  
  
  CONCLUSIONS
  The observed pattern of higher circulating PECAM(+) EMP levels links BAV disease to endothelial damage and aortic dilation. Circulating PECAM(+) EMPs were identified as a biological variable related to aortic dilation in patients with BAV disease.
authors.affiliation: Grup de Recerca Cardiovascular, Servei de Cardiologia, Hospital Universitari de Sant Joan, IISPV, Universitat Rovira i Virgili, Reus, Spain. Electronic address: josepmaria.alegret@urv.cat.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Alegret
authors.affiliation: Grup de Recerca Cardiovascular, Servei de Cardiologia, Hospital Universitari de Sant Joan, IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Neus
authors.initials: N
authors.lastname: Martínez-Micaelo
authors.affiliation: Grup de Recerca Cardiovascular, Servei de Cardiologia, Hospital Universitari de Sant Joan, IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Gerard
authors.initials: G
authors.lastname: Aragonès
authors.affiliation: Grup de Recerca Cardiovascular, Servei de Cardiologia, Hospital Universitari de Sant Joan, IISPV, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Beltrán-Debón
mesh_terms: D000328:Adult; D001018:Aortic Diseases / Q000378:metabolism / Q000473:pathology*; D001021:Aortic Valve / Q000002:abnormalities* / Q000378:metabolism / Q000473:pathology; D000082882:Bicuspid Aortic Valve Disease; D015415:Biomarkers / Q000097:blood; D004106:Dilatation; D019040:E-Selectin / Q000097:blood*; D005260:Female; D006349:Heart Valve Diseases / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008297:Male; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D019040:E-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C546936:SELE protein, human
keywords: Aortic dilation; Aortic root; Ascending aorta; Bicuspid aortic valve; Endothelial microparticles