Transforming growth factor β1 and coronary intimal hyperplasia in pediatric patients with congenital heart disease

Can J Cardiol. 2013 Jul;29(7):849-57. doi: 10.1016/j.cjca.2012.11.018. Epub 2013 Feb 6.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • 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*

Substances

  • Transforming Growth Factor beta1