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Idiopathic dilated cardiomyopathy exhibits defective vascularization and vessel formation.

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-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.

journal_name

Eur J Heart Fail

journal_title

European journal of heart failure

authors

Roura S,Planas F,Prat-Vidal C,Leta R,Soler-Botija C,Carreras F,Llach A,Hove-Madsen L,Pons Lladó G,Farré J,Cinca J,Bayes-Genis A

doi

10.1016/j.ejheart.2007.07.008

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

995-1002

issue

10

eissn

1388-9842

issn

1879-0844

pii

S1388-9842(07)00270-X

journal_volume

9

pub_type

杂志文章

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