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113 | 2014
Annuaire du Collège de France 2012-2013
Résumé des cours et travaux 113e année
Conférenciers invités

Understanding Vascular Endothelium

Michael A. Gimbrone
p. 907-908

Notes de la rédaction

M. Michael A. Gimbrone a été invité par l’Assemblée des professeurs sur proposition des Prs Pierre Corvol et Alain Prochiantz, pour deux conférences données les 17 et 24 mai 2013.

Texte intégral

Understanding Vascular Endothelium : Nature’s Container for Blood

1The entire cardiovascular system, from the chambers of the heart to the smallest capillaries of peripheral tissues, is lined by a single-cell-thick continuous layer—the vascular endothelium. For many years, this gossamer membrane was thought to function largely as an inert barrier, passively separating the reactive components of the circulating blood from the cells and connective tissue matrix of the various organs of the body. With the advent of endothelial cell culture, enabling its isolation and study under experimentally controlled conditions in vitro, a rich appreciation of the dynamic nature of endothelium has emerged. A source of potent bioactive substances, such as prostaglandins, nitric oxide, chemokines and growth factors, the endothelium “speaks” outward to circulating blood elements, such as leukocytes and platelets, and inward to pericytes and smooth muscle cells, modifying their behavior via paracrine signaling mechanisms important in local tissue homeostasis. In response to proinflammatory cytokines (e.g., interleukin-1 and tumor necrosis factor) and bacterial products (e.g., endotoxins), endothelial cells can undergo dramatic phenotypic modulation, manifested by the expression of inducible cell surface adhesion molecules that selectively recruit leukocytes as part of the immune/inflammatory response. Dysregulation of these reactive mechanisms can result in chronic pathologies, such as atherosclerosis and its thrombotic sequelae—heart attack and stroke. The application of high-throughput genomic analyses is revealing the underlying mechanisms of endothelial dysfunction, and pointing the way to new therapeutic strategies in cardiovascular disease.

Vascular Endothelium, Biomechanical Forces, and the Pathogenesis of Atherosclerosis

2The localization of atherosclerotic lesions to regions of disturbed blood flow associated with certain arterial geometries, in humans and experimental animals, suggests an important role for hemodynamic forces in the pathobiology of atherosclerosis. There is increasing evidence that the vascular endothelium, which is directly exposed to various fluid mechanical stimuli generated by pulsatile blood flow, can discriminate among these different biomechanical stimuli and transduce them into genetic regulatory programs that modulate endothelial function in health and disease. In this seminar, we will discuss how biomechanical stimuli generated by blood flow can influence endothelial functional phenotypes, and explore the working concept of “atheroprone” hemodynamic environments as “local risk factors” in atherogenesis. In addition, we will consider the therapeutic implications of the activation of “atheroprotective genes” and their role(s) as “critical regulatory nodes” in vascular hemostasis.

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Référence papier

Cours et travaux du Collège de France. Annuaire 113e année, Collège de France, Paris, avril 2014, p. 907-908. ISBN 978-2-7226-0329-5

Référence électronique

Michael A. Gimbrone, « Understanding Vascular Endothelium », L’annuaire du Collège de France [En ligne], 113 | 2014, mis en ligne le 15 août 2014, consulté le 27 mai 2018. URL : http://journals.openedition.org/annuaire-cdf/2766

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Auteur

Michael A. Gimbrone

Professeur, Harvard Medical School, Boston (États-Unis)

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Droits d’auteur

Collège de France

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