Pathophysiology of aortic aneurysm: insights from human genetics and mouse models

Abstract

Aneurysms are local dilations of an artery that predispose the vessel to sudden rupture. They are often asymptomatic and undiagnosed, resulting in a high mortality rate. The predisposition to develop thoracic aortic aneurysms is often genetically inherited and associated with syndromes affecting connective tissue homeostasis. This review discusses how elucidation of the genetic causes of syndromic forms of thoracic aortic aneurysm has helped identify pathways that contribute to disease progression, including those activated by TGF-β, angiotensin II and Notch ligands. We also discuss how pharmacological manipulation of these signaling pathways has provided further insight into the mechanism of disease and identified compounds with therapeutic potential in these and related disorders.

Keywords: ERK1/2; Loeys–Dietz syndrome; Marfan syndrome; Notch; Smad; TGF-β; aneurysm; angiotensin II; aorta; bicuspid aortic valve.