TGF-Beta1 and Estrogen Receptor Alpha in Coronary Intimal Hyperplasia in Pediatric Patients with Congenital Heart Disease

CASTILLA R.; OTERO-LOSADA, M.; MULLER ANGELICA; AZZATO F.; AMBROSIO G.; MILEI J.

Congenital Heart Diseases: An Updated Approach to Some Important Issues.

Nova Science Publishers, Inc.

Lugar: New York; Año: 2014; p. 17 - 36

Congenital heart defects (CHD) and/ or their repair process lead to an increased risk for adult cardiovascular disease compared with the general population. Intimal hyperplasia is a pre-atherosclerotic lesion that may be produced as a consequence of the activation of transforming growth factor beta-1 (TGF-β1) pathway or ERα inhibition. This chapter deals with our recent findings in this regard and comments our latest results in connection with relevant reports from other authors. We examined the coronary arteries from a pediatric population with CHD and evaluated the possible relationship between the frequency of intimal hyperplasia and the magnitude of TGF-β1 in order to enlighten the possible role of TGF-β1 in the genesis of these lesions. The coronary arteries of 10 control patients and 98 CHD patients (54% cyanotic type, 32% surgically repaired) were stained and assessed for the presence and degree of intimal thickening. The expression of TGF-β1 and ERα was determined by immunohistochemical examination. The frequency of coronary intimal hyperplasia did not depend on the group, i.e.: cyanotic CHD group (66%) and non-cyanotic CHD group (64%). However, the frequency of coronary intimal hyperplasia was higher in patients with surgically repaired CHD than in patients without surgical intervention (80% vs. 47% respectively, p=0.0002). The degree of positive immunostaining for TGF-β1 or ERα did not depend on the group. i.e.: cyanotic and non-cyanotic type. On the other hand, examination of the intimal layer showed that TGF-ß1 expression was higher and expression of ERα was smaller in patients with surgically repaired CHD compared with those without surgery. The relationship between the frequency of intimal hyperplasia and the expression of TGF-β1 and ERα in arteries from 98 pediatric patients with congenital heart defects indicated that: 1) intimal hyperplasia was a common finding in the coronary tree of these patients, 2) both TGF-β1 and ERα seemed to play a major role in this phenomenon and 3) surgical correction of CHD was associated with further coronary vascular remodeling.