Estrogen receptor alpha in coronary intimal thickenings in pediatric patients with congenital heart disease

CASTILLA, ROCÍO; GUERRI-GUTTEMBERG, ROBERTO A; MULLER, ANGÉLICA; OTERO-LOSADA, MATILDE; MILEI, JOSÉ

Munich

Congreso; ESC Congress 2012; 2012

Sociedad Europea de Cardiología

PURPOSE. Congenital heart defects (CHD) and/or the repair process increase the incidence of coronary atheroma. Initial lesions of coronary arteries are characterizedby intimal smooth muscle cells (SMCs) proliferation causing intimal thickening prior to lipid deposition. Considering that estrogen receptor alpha (ER7) stimulationinhibits SMCs proliferation and migration, this work aimed to evaluate the possible involvement of ER7 in coronary intimal hyperplasia in CHD. METHODS. Fifty sevennecropsies of CHD patients (mean age 2.4 years, 29 male) were included. Twenty-two (39 %) of the patients, mostly Tetralogy of Fallot, had undergone surgical repair.Four samples 3 mm width, taken from the left main, right, circumflex and posterior interventricular coronary arteries, were embedded in paraffin and serially sectionedand used for ER7 immunohistochemistry (anti-ER7, MC-20, Santa Cruz Biotechnology, Inc, CA, USA. Image J software, NIH, Bethesda, USA). GraphPad Prism v 5.03and IBM SPSS Statistics 19 software were used for data analysis and plotting. RESULTS. Estrogen receptor alpha was expressed in SMCs of media, endothelium andintimal thickenings. The percentage of Immunopositive ER7 area in the whole artery and the media and intima layers was not dependent on sex. Yet, a sustainedtendency to larger ER7 areas was observed in female compared to male cells in all 3 conditions. Surgery reduced the percentage of immunopositive ER7 area in theintima layer (p=0.029) and in the whole artery (p=0.016) as well. CONCLUSION. Surgery reduced ER7 density in the intima layer and in the whole artery. ER7inhibition after surgical ischemia-reperfusion might interfere with a variety of rapid intracellular signaling cascades and induce SMCs proliferation/migration and intimalthickening.