title: Role of mechanotransduction in vascular biology: focus on thoracic aortic aneurysms and dissections.
abstract: Thoracic aortic diseases that involve progressive enlargement, acute dissection, or rupture are influenced by the hemodynamic loads and mechanical properties of the wall. We have only limited understanding, however, of the mechanobiological processes that lead to these potentially lethal conditions. Homeostasis requires that intramural cells sense their local chemomechanical environment and establish, maintain, remodel, or repair the extracellular matrix to provide suitable compliance and yet sufficient strength. Proper sensing, in turn, necessitates both receptors that connect the extracellular matrix to intracellular actomyosin filaments and signaling molecules that transmit the related information to the nucleus. Thoracic aortic aneurysms and dissections are associated with poorly controlled hypertension and mutations in genes for extracellular matrix constituents, membrane receptors, contractile proteins, and associated signaling molecules. This grouping of factors suggests that these thoracic diseases result, in part, from dysfunctional mechanosensing and mechanoregulation of the extracellular matrix by the intramural cells, which leads to a compromised structural integrity of the wall. Thus, improved understanding of the mechanobiology of aortic cells could lead to new therapeutic strategies for thoracic aortic aneurysms and dissections.
authors: From the Departments of Biomedical Engineering (J.D.H., M.A.S.), Medicine (Cardiology) (M.A.S.), Cell Biology (M.A.S.), and Surgery (G.T.), Yale University, New Haven, CT; and Department of Internal Medicine, University of Texas Health Science Center, Houston (D.M.M.).
authors: Jay D
authors: JD
authors: Humphrey
authors: From the Departments of Biomedical Engineering (J.D.H., M.A.S.), Medicine (Cardiology) (M.A.S.), Cell Biology (M.A.S.), and Surgery (G.T.), Yale University, New Haven, CT; and Department of Internal Medicine, University of Texas Health Science Center, Houston (D.M.M.).
authors: Martin A
authors: MA
authors: Schwartz
authors: From the Departments of Biomedical Engineering (J.D.H., M.A.S.), Medicine (Cardiology) (M.A.S.), Cell Biology (M.A.S.), and Surgery (G.T.), Yale University, New Haven, CT; and Department of Internal Medicine, University of Texas Health Science Center, Houston (D.M.M.).
authors: George
authors: G
authors: Tellides
authors: From the Departments of Biomedical Engineering (J.D.H., M.A.S.), Medicine (Cardiology) (M.A.S.), Cell Biology (M.A.S.), and Surgery (G.T.), Yale University, New Haven, CT; and Department of Internal Medicine, University of Texas Health Science Center, Houston (D.M.M.). dianna.m.milewicz@uthsc.tmc.edu.
authors: Dianna M
authors: DM
authors: Milewicz
mesh_terms: D000784:Aortic Dissection / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D001019:Aortic Rupture / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D001696:Biomechanical Phenomena; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006439:Hemodynamics; D006801:Humans; D040542:Mechanotransduction, Cellular; D010641:Phenotype; D013314:Stress, Mechanical
chemical_list: D016326:Extracellular Matrix Proteins
keywords: Marfan syndrome; actomyosin; elastic fibers; focal adhesion