Therapeutics Targeting Drivers of Thoracic Aortic Aneurysms and Acute Aortic Dissections: Insights from Predisposing Genes and Mouse Models
Year: 2017
Type: review
Abstract: Thoracic aortic diseases, including aneurysms and dissections of the thoracic aorta, are a major cause of morbidity and mortality. Risk factors for thoracic aortic disease include increased hemodynamic forces on the ascending aorta, typically due to poorly controlled hypertension, and heritable genetic variants. The altered genes predisposing to thoracic aortic disease either disrupt smooth muscle cell (SMC) contraction or adherence to an impaired extracellular matrix, or decrease canonical transforming growth factor beta (TGF-β) signaling. Paradoxically, TGF-β hyperactivity has been postulated to be the primary driver for the disease. More recently, it has been proposed that the response of aortic SMCs to the hemodynamic load on a structurally defective aorta is the primary driver of thoracic aortic disease, and that TGF-β overactivity in diseased aortas is a secondary, unproductive response to restore tissue function. The engineering of mouse models of inherited aortopathies has identified potential therapeutic agents to prevent thoracic aortic disease.
Source: Annual Review of Medicine
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: Center for Clinical and Translational Sciences (CCTS), Mutations in Smooth Muscle Contractile Proteins: Pathways to Vascular Diseases, Characterization of a novel pathway of aortic aneurysm formation., Genetic Predisposition To Thoracic Aortic Aneurysms/Dissections, Mouse Models for Systems Therapeutics Degenerative Diseases
OpenAlex ID: W2572871393