Idiopathic dilated cardiomyopathy exhibits defective vascularization and vessel formation

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 (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