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.


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-1alpha and beta-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-1alpha(+) 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 beta-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.
Roura
Santiago
S
Cardiology Service-Institut Català de Ciencies Cardiovasculars, Hospital Santa Creu i Sant Pau, Barcelona, Spain.
Planas
Francesc
F
Prat-Vidal
Cristina
C
Leta
Ruben
R
Soler-Botija
Carolina
C
Carreras
Francesc
F
Llach
Anna
A
Hove-Madsen
Leif
L
Pons Lladó
Guillem
G
Farré
Jordi
J
Cinca
Juan
J
Bayes-Genis
Antoni
A
D000328:Adult; D015415:Biomarkers; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000503:physiopathology*; D016022:Case-Control Studies; D016207:Cytokines; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D013234:Stem Cells / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin / Q000502:physiology*
D015415:Biomarkers; D016207:Cytokines; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin