Physiopathologie du remodelage artériel dans l'hypertension artérielle

Abstract

Il existe schématiquement deux types de modifications artérielles en réponse à l’hypertension, capables toutes deux de diminuer la lumière artérielle : l’hypertrophie, avec augmentation du volume de la paroi, et le remodelage, où le volume pariétal n’est pas modifié. Ces dernières années, le remodelage artériel s’est imposé comme un concept clé de la physiopathologie de l’hypertension artérielle, source de multiples applications pharmacologiques. La meilleure connaissance des modifications ultrastructurales et géométriques dans les artères de gros, moyen et petit calibre (artères résistives) a modifié leur approche thérapeutique en offrant de nouvelles cibles pharmacologiques : facteurs de croissance et récepteurs spécifiques divers des cellules musculaires lisses et endothéliales, récepteurs et enzymes de la matrice extracellulaire.

In recent years, arterial remodeling emerged as a key concept for the understanding of the pathogenesis of arterial hypertension, with numerous pharmacological applications. The concept of remodeling, advanced by Baumbach and Heistad in 1988, states that, during hypertension, the structural changes in the resistance vessels may not be associated with net growth. Experiments in genetically hypertensive rats and essential hypertensive patients have shown that the increase in arteriolar resistance to blood flow is due to structural changes which can be described not by net growth but by a process or rearrangement of otherwise normal material. Later, the term 'vascular remodeling' was used by Gibbons and Dzau to describe any 'active process of structural alteration that involves changes in at least four cellular process - cell growth, cell death, cell migration, and production of extra-cellular matrix - and is dependent on a dynamic interaction between locally generated growth factors, vasoactive substances, and hemodynamic stimuli'. Remodeling may thus contribute to the pathophysiology of various large and small artery diseases including not only hypertension but also heart failure, atherosclerosis, restenosis after angioplasty, and pulmonary hypertension. The present review will discuss the ultrastructural and geometrical changes in large and small arteries of hypertensive humans and animals, described as 'remodeling', and their functional consequences, both at the site of conducting arteries (potentiation of atherosclerosis and autoregulation of arterial compliance) and resistive arteries (structural increase in peripheral vascular resistance, hyperreactivity to arteriolar stimuli, decrease in the perfusion reserve of target organs, and modifications of the autoregulation of regional blood flow). [References: 56]