Plasma cholesterol concentration and cigarette smoking have been well established as the major exogenous risk factors for the development of atherosclerosis. The observations reported in the literature regarding the fetal origin of coronary artery lesions are rare and controversial.Aim: To identify the features of early atherosclerotic coronary artery lesions in late fetal stillborns and infants and the possible atherogenic role of maternal cigarette smoking. Methods: We examined 22 unexpected fetal deaths and 36 sudden infant death syndrome victims, all between 32nd week of gestation and one year of age. All underwent autopsy. In 28/58 of the cases the mothers were smokers before and during pregnancy. The four major epicardial coronary arteries were isolated along their whole length, embedded in paraffin and serially cut for histologic examination. The sections were stained with hematoxylin-eosin, Heidenahin trichromic (Azan), Alcian blue (pH 0.5 and 2.5) and Weigert, and immunohistochemical studies, for CD68, CD34, anti-actin, PCNA, c-fos expression, and apoptosis (TUNEL method). Results: In 10/12 of fetuses and in 15/16 of infants of smoking mothers, multifocal coronary lesions of varying entity were detected. Only in 5 cases (2/10 fetus and 3/20 infants) arterial lesions were observed in infants with non-smoker mother (p<0.0001). The alterations ranged from focal areas with mild myointimal thickening in prenatal life to early soft parietal plaques in infants, partially reducing the arterial lumen up to 30-40%. The smooth muscle cells (SMCs) presented loss of polarity, forming columns perpendicular to the axis of the media and infiltrating the subendothelial connective tissue, mostly with rupture of the internal elastic lamina. Increased amounts of mucoid ground substance were also observed at this level. Macrophages were detected in the intimal border of the lesions, penetrating the endothelium. No neoangiogenesis was observed. These early atherosclerotic lesions, presented c-fos gene activation in the SMCs of the tunica media, and in some of these, positivity of the SMCs for apoptosis was also observed; suggesting that c-fos gene over-expression could promote a proliferative process, as testified by the PCNA positivity.Conclusion: Early intimal alterations of the coronary arteries are already detectable in the prenatal period and are significantly associated with maternal cigarette smoking.

Immunotypification of perinatal and infant early atherosclerotic coronary lesions / L. Matturri, G. Ottaviani, A.M. Lavezzi, D.R. Grana, J. Milei. - In: EUROPEAN HEART JOURNAL. - ISSN 0195-668X. - 26:Suppl. 1(2005), pp. 11-11. ((Intervento presentato al convegno ESC European Society of Cardiology Congress 2005 September 3-7, 2005. Stockholm, Sweden tenutosi a Stockholm, Sweden nel 2005 [10.1093/eurheartj/ehi020].

Immunotypification of perinatal and infant early atherosclerotic coronary lesions

L. Matturri
Primo
;
G. Ottaviani
Secondo
;
A.M. Lavezzi;
2005

Abstract

Plasma cholesterol concentration and cigarette smoking have been well established as the major exogenous risk factors for the development of atherosclerosis. The observations reported in the literature regarding the fetal origin of coronary artery lesions are rare and controversial.Aim: To identify the features of early atherosclerotic coronary artery lesions in late fetal stillborns and infants and the possible atherogenic role of maternal cigarette smoking. Methods: We examined 22 unexpected fetal deaths and 36 sudden infant death syndrome victims, all between 32nd week of gestation and one year of age. All underwent autopsy. In 28/58 of the cases the mothers were smokers before and during pregnancy. The four major epicardial coronary arteries were isolated along their whole length, embedded in paraffin and serially cut for histologic examination. The sections were stained with hematoxylin-eosin, Heidenahin trichromic (Azan), Alcian blue (pH 0.5 and 2.5) and Weigert, and immunohistochemical studies, for CD68, CD34, anti-actin, PCNA, c-fos expression, and apoptosis (TUNEL method). Results: In 10/12 of fetuses and in 15/16 of infants of smoking mothers, multifocal coronary lesions of varying entity were detected. Only in 5 cases (2/10 fetus and 3/20 infants) arterial lesions were observed in infants with non-smoker mother (p<0.0001). The alterations ranged from focal areas with mild myointimal thickening in prenatal life to early soft parietal plaques in infants, partially reducing the arterial lumen up to 30-40%. The smooth muscle cells (SMCs) presented loss of polarity, forming columns perpendicular to the axis of the media and infiltrating the subendothelial connective tissue, mostly with rupture of the internal elastic lamina. Increased amounts of mucoid ground substance were also observed at this level. Macrophages were detected in the intimal border of the lesions, penetrating the endothelium. No neoangiogenesis was observed. These early atherosclerotic lesions, presented c-fos gene activation in the SMCs of the tunica media, and in some of these, positivity of the SMCs for apoptosis was also observed; suggesting that c-fos gene over-expression could promote a proliferative process, as testified by the PCNA positivity.Conclusion: Early intimal alterations of the coronary arteries are already detectable in the prenatal period and are significantly associated with maternal cigarette smoking.
Cardiorenal connection; Heart failure; Renal function; Severe cardiorenal syndrome
Settore MED/08 - Anatomia Patologica
2005
European Society of Cardiology
http://spo.escardio.org/AbstractDetails.aspx?id=22772&eevtid=11
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/46266
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