Transforming Growth Factor β1 and Coronary Intimal Hyperplasia in Pediatric Patients With Congenital Heart Disease

• Published in: Canadian journal of cardiology 2013-07, Vol.29 (7), p.849-857
• Main Authors: Guerri-Guttenberg, Roberto A., MD, PhD, Castilla, Rocío, ScD, PhD, Francos, Gabriela C., MD, Müller, Angélica, MSc, Ambrosio, Giuseppe, MD, PhD, Milei, José, MD, PhD
• Format: Article
• Language: English
• Subjects: Adolescent; Cardiovascular; Case-Control Studies; Child; Child, Preschool; Coronary Vessels - metabolism; Coronary Vessels - pathology; Female; Heart Defects, Congenital - metabolism; Heart Defects, Congenital - surgery; Humans; Hyperplasia - etiology; Hyperplasia - metabolism; Immunohistochemistry; Infant; Infant, Newborn; Male; Prevalence; Transforming Growth Factor beta1 - metabolism; Tunica Intima - metabolism; Tunica Intima - pathology
• ISSN: 0828-282X; 1916-7075
• DOI: 10.1016/j.cjca.2012.11.018

Abstract Background Congenital heart defects or the process of their repair leads to an increased risk for adult cardiovascular disease compared with the general population. Intimal hyperplasia is a preatherosclerotic lesion that may be produced as a consequence of transforming growth factor β1 (TGF-β1) pathway activation. We studied the presence of intimal hyperplasia in arteries from a pediatric population with congenital heart disease (CHD) and TGF-β1 expression to enlighten its possible role in the genesis of these lesions. Methods Coronary arteries from 10 controls and 98 CHD patients (54% cyanotic type, 32% surgically repaired) were stained, and the presence and degree of intimal thickening were analyzed. The expression of TGF-β1 was studied by immunohistochemistry. Results The difference between the presence of coronary intimal hyperplasia in patients with cyanotic (35; 66.1%) and noncyanotic CHD (29; 64.3%) was not significant. However, surgically repaired CHD presented a higher rate of coronary intimal hyperplasia (80%) than did the group without surgical intervention (47.3%), P  = 0.0002. The immunostaining for TGF-β1 analyzed in samples of patients with cyanotic and noncyanotic CHD showed no significant differences. However, TGF-β1 expression was more intense on the intimal layer of patients with surgically repaired CHD than on that of those without surgery (intimal area positive for TGF-β1, 50.43% vs 15.91%, respectively; Mann-Whitney U test P  = 0.0005). Conclusion The high incidence of intimal hyperplasia in patients with surgically repaired CHD is correlated with TGF-β1 expression and may contribute to the development of atherosclerotic coronary artery disease in CHD patients.