Idiopathic dilated cardiomyopathy exhibits defective vascularization and vessel formation

Santiago Roura, Francesc Planas, Cristina Prat-Vidal, Ruben Leta, Carolina Soler-Botija, Francesc Carreras, Anna Llach, Leif Hove-Madsen, Guillem Pons Lladó, Jordi Farré, Juan Cinca, Antoni Bayes-Genis

Research output: Contribution to journalArticleResearchpeer-review

46 Citations (Scopus)

Abstract

Background: Ultrastructural findings of idiopathic dilated cardiomyopathy (IDCM) include myocyte atrophy and myofilament loss, yet little is known about the vascular abnormalities present in IDCM. Methods and results: Patients with IDCM and controls underwent multi-slice CT to examine length and diameter of epicardial vasculature. The levels of mobilizing cytokines and circulating EPCs were assessed by endothelial colony formation assay and flow cytometry. Immunohistochemistry and Western blot were used to examine microvessel density and expression of HIF-1α and β-catenin. Main epicardial coronary arteries were shorter and smaller, and microvascular density was reduced in the epicardium in IDCM. Epicardial vessel paucity was associated with increased numbers of HIF-1α+ cells (46.8 ± 13.1% vs. 19.4 ± 9.4%, p = 0.006) indicating local epicardial hypoxia and elevation of circulating VEGF-A (394 pg/mL vs. 22 pg/mL, p = 0.001). The number of mobilized progenitors CD133+/VEGF-R2+ was 21-fold higher in IDCM compared with controls (6.5 ± 3.3% vs. 0.3 ± 0.2%; p < 0.001). Moreover, this defective vascularization was associated with reduced myocardial expression of vascular β-catenin, an important angiogenic regulator. Conclusions: This study shows defective vascularization and impaired vasculogenesis (the de novo vascular organization of mobilized endothelial progenitors) and angiogenesis (by which new blood vessels are formed from pre-existing mature endothelial cells) in human IDCM. © 2007 European Society of Cardiology.
Original languageEnglish
Pages (from-to)995-1002
JournalEuropean Journal of Heart Failure
Volume9
Issue number10
DOIs
Publication statusPublished - 1 Oct 2007

Keywords

  • β-catenin
  • Angiogenesis
  • EPC
  • Idiopathic dilated cardiomyopathy
  • Multi-slice CT
  • Vasculogenesis

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