Biology of vascular wall dilation and rupture

Author:

Michel Jean-Baptiste

Abstract

Arterial pathologies, important causes of death and morbidity in humans, are closely related to modifications in the circulatory system during evolution. With increasing intraluminal pressure and arterial bifurcation density, the arterial wall becomes the target of interactions with blood components and outward convection of plasma solutes and particles, including plasma zymogens and leukocyte proteases. Abdominal aortic aneurysms of atherothrombotic origin are characterized by the presence of an intraluminal thrombus (ILT), a major source of proteases, including plasmin, MMP-9, and elastase. Saccular cerebral aneurysms are characterized by the interaction of haemodynamics and arterial bifurcation defects, of either genetic or congenital origin. They also develop an intrasaccular thrombus, implicated in rupture. Aneurysms of the ascending aorta (TAAs) are not linked to atherothrombotic disease, and do not develop an ILT. The most common denominator of TAAs, whatever their aetiology, is the presence of areas of mucoid degeneration, and increased convection and vSMC-dependent activation of plasma zymogens within the wall, causing extracellular matrix proteolysis. TAA development is also associated with an epigenetic phenomenon of SMAD2 overexpression and nuclear translocation, potentially linked to chronic changes in mechanotransduction. Aortic dissections share common aetiologies and pathology (areas of mucoid degeneration) with TAAs, but differ by the absence of any compensatory epigenetic response. There are main experimental animal models of aneurysms, all characterized by the cessation of aneurysmal progression after interruption of the exogenous stimuli used to induce it. These new pathophysiological approaches to aneurysms in humans pave the way for new diagnostic and therapeutic tools.

Publisher

Oxford University Press

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