The metabolic rate of the arterial wall depends on the process of filtration of nutrient substances, as capillaries are largely absent in the wall. Therefore, by altering the filtration process, the deposition of lipids favors yet further deposition, creating a vicious circle. In these conditions, the morphological picture is characterized by the accumulation of passive lipid deposits that predominate over the cell defense reactions. The reaction of the smooth muscle cells (SMCs) of the tunica media is considered to be secondary to the above process, contributing to the phagocytic and intimal thickening processes. Thus, the myocytic reaction is not attributed a significant weight in the birth of the atherosclerotic process. Results of our research on the harmful effects of cigarette smoke, in particular, on the arterial wall have contributed to better delineate the morpho-functional picture of onset and development of atherosclerosis. In the fetal arteries, the reaction powers of the SMCs are especially marked. In these conditions, our observations have demonstrated that surprisingly, in fetuses of smoking mothers, the very first defense reaction is morphological alteration of the architecture of the tunica media. In absence of morphologically apparent lesions of the endothelium and subendothelial connective tissue, the early morphologically observable alteration is the appearance of columns of cells running down from the muscular tunica and perpendicularly infiltrating the intima, as if attempting to block penetration of the molecules of the gaseous products circulating in the blood. These histopathological alterations are associated with marked changes in the biological homeostasis of the SMCs. Our molecular biology studies have, in fact, revealed that the first biological reaction in these cells caused by the gaseous products of nicotine combustion is intense activation of the c-fos proto-oncogene. This gene belongs to the family of “Immediate Early Genes”, so defined because of their characteristically rapid activation in response to various injuries, due to the fact that they do not require protein synthesis. In addition, the SMCs are transformed from the contractile or quiescent phenotype, characterized by the presence of α-actin, into the synthetic or activated type, showing loss of the contractile function and a switch in actin expression from the α- to the β-form, a protein usually expressed by fibroblasts. Activated SMCs, or myofibroblasts, start to produce collagen, elastin and extracellular matrix material and reacquire the primordial characteristic of ameboid movement, enabling them to leave the media, which appears subverted and thinned, and to move through the intima towards the lumen. The biological evolution of the lesions is characterized by the maintenance of a delicate balance between cell proliferation and apoptosis of the SMCs and the beginning of cytogenetic alterations, in particular trisomy of chromosome 7, so that the atherosclerotic process resembles that of a benign tumor. These observations have allowed us to interpret the atherosclerotic process not, as previously believed, as the consequence of a passive accumulation of lipid materials, first in the intima and then in the media of an arterial wall lacking the ability to react. The atherosclerosis is the expression of the reaction of myofibroblasts to the action of harmful agents. During evolution of the condition, if there is continual deposition of lipid substances, these will predominate and foster an overwhelming monocytic infiltration. Our observations of atherosclerotic lesions in victims of non-smoking mothers have led us to believe that yet other risk factors may play a role contributing to trigger arterial wall alterations. Since most of the subjects of our studies lived in large industrialized cities, we can hypothesize that air pollution could also exert an atherogenic effect.

Natural history of perinatal coronary atherosclerosis / L. Matturri, G. Ottaviani, A.M. Lavezzi - In: Progress in Coronary Artery Disease - Proceedings of the 6th International Congress on Coronary Artery Disease / B.S. Lewis, Z. Ongen, M.Y. Flugelman, D.A. Halon. - Bologna : Monduzzi editore ; Medimond publishing company, 2005 Oct. - ISBN 88-7587-200-7. - pp. 67-70 (( Intervento presentato al 6. convegno International Congress on Coronary Artery Disease : from Prevention to Intervention, 2005 October 29th-November 1st tenutosi a Istanbul, Turkey nel 2005, October 29th-November 1st.

Natural history of perinatal coronary atherosclerosis

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

Abstract

The metabolic rate of the arterial wall depends on the process of filtration of nutrient substances, as capillaries are largely absent in the wall. Therefore, by altering the filtration process, the deposition of lipids favors yet further deposition, creating a vicious circle. In these conditions, the morphological picture is characterized by the accumulation of passive lipid deposits that predominate over the cell defense reactions. The reaction of the smooth muscle cells (SMCs) of the tunica media is considered to be secondary to the above process, contributing to the phagocytic and intimal thickening processes. Thus, the myocytic reaction is not attributed a significant weight in the birth of the atherosclerotic process. Results of our research on the harmful effects of cigarette smoke, in particular, on the arterial wall have contributed to better delineate the morpho-functional picture of onset and development of atherosclerosis. In the fetal arteries, the reaction powers of the SMCs are especially marked. In these conditions, our observations have demonstrated that surprisingly, in fetuses of smoking mothers, the very first defense reaction is morphological alteration of the architecture of the tunica media. In absence of morphologically apparent lesions of the endothelium and subendothelial connective tissue, the early morphologically observable alteration is the appearance of columns of cells running down from the muscular tunica and perpendicularly infiltrating the intima, as if attempting to block penetration of the molecules of the gaseous products circulating in the blood. These histopathological alterations are associated with marked changes in the biological homeostasis of the SMCs. Our molecular biology studies have, in fact, revealed that the first biological reaction in these cells caused by the gaseous products of nicotine combustion is intense activation of the c-fos proto-oncogene. This gene belongs to the family of “Immediate Early Genes”, so defined because of their characteristically rapid activation in response to various injuries, due to the fact that they do not require protein synthesis. In addition, the SMCs are transformed from the contractile or quiescent phenotype, characterized by the presence of α-actin, into the synthetic or activated type, showing loss of the contractile function and a switch in actin expression from the α- to the β-form, a protein usually expressed by fibroblasts. Activated SMCs, or myofibroblasts, start to produce collagen, elastin and extracellular matrix material and reacquire the primordial characteristic of ameboid movement, enabling them to leave the media, which appears subverted and thinned, and to move through the intima towards the lumen. The biological evolution of the lesions is characterized by the maintenance of a delicate balance between cell proliferation and apoptosis of the SMCs and the beginning of cytogenetic alterations, in particular trisomy of chromosome 7, so that the atherosclerotic process resembles that of a benign tumor. These observations have allowed us to interpret the atherosclerotic process not, as previously believed, as the consequence of a passive accumulation of lipid materials, first in the intima and then in the media of an arterial wall lacking the ability to react. The atherosclerosis is the expression of the reaction of myofibroblasts to the action of harmful agents. During evolution of the condition, if there is continual deposition of lipid substances, these will predominate and foster an overwhelming monocytic infiltration. Our observations of atherosclerotic lesions in victims of non-smoking mothers have led us to believe that yet other risk factors may play a role contributing to trigger arterial wall alterations. Since most of the subjects of our studies lived in large industrialized cities, we can hypothesize that air pollution could also exert an atherogenic effect.
perinatal coronary atherosclerosis ; maternal cigarette smoking ; air pollution
Settore MED/08 - Anatomia Patologica
ott-2005
Book Part (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/16510
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