© 2007 European Society of Cardiology
Idiopathic dilated cardiomyopathy exhibits defective vascularization and vessel formation
a Cardiology Service-Institut Català de Ciencies Cardiovasculars, Hospital Santa Creu i Sant Pau Barcelona, Spain
b Cardiology Service, Hospital Santa Creu i Sant Pau Barcelona, Spain
c Departament de Medicina, Universitat Autònoma de Barcelona Barcelona, Spain
* Corresponding author. Cardiology Service-ICCC, Hospital de la Santa Creu i Sant Pau, Departament de Medicina (Universitat Autónoma de Barcelona) C/ Sant Antoni Ma Claret 167, 08025 Barcelona, Spain. Tel.: +34 93 291 92 58; fax: +34 93 291 94 24. E-mail address: abayesgenis{at}santpau.es (A. Bayes-Genis).
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Abstract |
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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-1
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-1+ cells (46.8±13.1% vs. 19.4±9.4%, p=0.006) indicating local epicardial hypoxia and elevation of circulating VEGF-A (394pg/mL vs. 22pg/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.
Key Words: Idiopathic dilated cardiomyopathy • Vasculogenesis • Angiogenesis • Multi-slice CT • EPC • β-catenin
Received April 25, 2007; Revised May 22, 2007; Accepted July 5, 2007
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