title: New insights into molecular mechanisms of diffuse coronary ectasiae: a possible role for VEGF.
abstract: BACKGROUND
  Diffuse coronary artery ectasiae (DCE) are occasionally found at necropsy or at angiography. Pathogenetic mechanisms of DCE are still poorly known. Matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs) and vascular endothelial growth factor (VEGF) are involved in vascular remodeling and may play a role in DCE.
  
  
  METHODS
  A total of 1280 consecutive coronary angiograms performed in a single institution in 1 year were screened. DCE were found in 15 patients. Diagnosis at hospital admission was acute coronary syndromes in all of them. Two patients died during initial admission and 1 refused blood sampling; the remaining 12 patients were enrolled in the study. No patient with DCE exhibited coronary stenoses. Plasma levels of VEGF, MMP-2, TIMP-1, TIMP-2 and C-reactive protein (CRP) were measured in these 12 patients 12 months after discharge during a silent clinical phase, in 12 age- and sex-matched patients with stable angina (SA) and coronary artery disease, and in 12 age- and sex-matched patients with normal coronary arteries (NCA).
  
  
  RESULTS
  VEGF levels were higher in patients with DCE than in SA or NCA (151.6 pg/ml [36.2-252.9] vs. 66.6 pg/ml [36.4-93.3] and 54.8 pg/ml [14.5-87.1], respectively, p = 0.012]. TIMP-2 levels were lower in DCE and SA than in NCA (5.9 ng/ml [0-33.6] and 5.0 [0-17.4] vs. 139.3 ng/ml [114.4-237.4], respectively, p < 0.001). TIMP-1 and MMP-2 plasma levels were similar in all groups (p = NS), and CRP levels were within normal limits (< 3 mg/L) in most patients, irrespective of their coronary anatomy (75% for DCE, 66% for SA, and 84% for NCA [p = NS]).
  
  
  CONCLUSIONS
  Symptomatic patients with DCE typically present with an acute coronary syndrome and exhibit lack of obstructive stenosis at angiography, decreased plasma levels of TIMP-2 and raised plasma levels of VEGF. The simultaneous occurrence of reduced MMPs inhibition and increased angiogenetic activity suggests an accelerated and persistent extracellular matrix remodeling process favouring arterial remodeling and aneurysms formation which is likely to enhance the risk of thrombosis because of low shear stress.
authors.affiliation: Institute of Cardiology, Catholic University of the Sacred Heart, Largo A. Gemelli 8, 00168 Rome, Italy.
authors.forename: Marinica
authors.initials: M
authors.lastname: Savino
authors.forename: Quintino
authors.initials: Q
authors.lastname: Parisi
authors.forename: Giuseppe G L
authors.initials: GG
authors.lastname: Biondi-Zoccai
authors.forename: Christian
authors.initials: C
authors.lastname: Pristipino
authors.forename: Domenico
authors.initials: D
authors.lastname: Cianflone
authors.forename: Filippo
authors.initials: F
authors.lastname: Crea
mesh_terms: D000328:Adult; D000368:Aged; D003323:Coronary Aneurysm / Q000097:blood / Q000175:diagnosis; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D004108:Dilatation, Pathologic / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D008875:Middle Aged; D012189:Retrospective Studies; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood*
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2