Between Rho(k) and a hard place: the relation between vessel wall stiffness, endothelial contractility, and cardiovascular disease.
نویسندگان
چکیده
Vascular stiffness is a mechanical property of the vessel wall that affects blood pressure, permeability, and inflammation. As a result, vascular stiffness is a key driver of (chronic) human disorders, including pulmonary arterial hypertension, kidney disease, and atherosclerosis. Responses of the endothelium to stiffening involve integration of mechanical cues from various sources, including the extracellular matrix, smooth muscle cells, and the forces that derive from shear stress of blood. This response in turn affects endothelial cell contractility, which is an important property that regulates endothelial stiffness, permeability, and leukocyte-vessel wall interactions. Moreover, endothelial stiffening reduces nitric oxide production, which promotes smooth muscle cell contraction and vasoconstriction. In fact, vessel wall stiffening, and microcirculatory endothelial dysfunction, precedes hypertension and thus underlies the development of vascular disease. Here, we review the cross talk among vessel wall stiffening, endothelial contractility, and vascular disease, which is controlled by Rho-driven actomyosin contractility and cellular mechanotransduction. In addition to discussing the various inputs and relevant molecular events in the endothelium, we address which actomyosin-regulated changes at cell adhesion complexes are genetically associated with human cardiovascular disease. Finally, we discuss recent findings that broaden therapeutic options for targeting this important mechanical signaling pathway in vascular pathogenesis.
منابع مشابه
Retraction note: Association between T-786C polymorphism of endothelial nitric oxide synthase gene and level of the vessel dilation factor in patients with coronary artery disease
متن کامل
Association between T-786C polymorphism of endothelial nitric oxide synthase gene and level of the vessel dilation factor in patients with coronary artery disease
Various polymorphisms on endothelial nitric oxide synthase (eNOs) gene cause reduced production of NO, the endothelial relaxing factor, and may accelerate the process of atherosclerosis. The study designed to investigate the frequency of T-786C polymorphism of the eNOs gene in patients suffering from coronary artery disease (CAD) in north-west of Iran. One hundred twenty subjects including 60 p...
متن کاملStudy of Pulsatile Non-Newtonian Blood Flow Through Abdominal Aorta and Renal Arteries Incorporating Fluid- Structure Interaction
Background: The interaction between the blood and the vessel wall is of great clinical interest in studying cardiovascular diseases, the major causes of death in developed countries.Objective: To understand the effects of incorporating fluid-structure interaction into the simulation of blood flow through an anatomically realistic model of abdominal aorta and renal arteries reconstructed from CT...
متن کاملAge-related intimal stiffening enhances endothelial permeability and leukocyte transmigration.
Age is the most significant risk factor for atherosclerosis; however, the link between age and atherosclerosis is poorly understood. During both aging and atherosclerosis progression, the blood vessel wall stiffens owing to alterations in the extracellular matrix. Using in vitro and ex vivo models of vessel wall stiffness and aging, we show that stiffening of extracellular matrix within the int...
متن کاملI-28: Role of Mevalonate-Ras Homology (Rho)/Rho-Associated Coiled-Coil-Forming Protein Ki nase-Mediated Signaling Pathway in The Pathogenesis of Endometriosis-Associated Fibrosis
Background: Endometriosis, a disease affecting 3-10% of women of reproductive age, is characterized by the ectopic growth of endometrial glands and stroma surrounded by dense fibrous tissue. Whereas, normal eutopic endometrium shows scarless tissue repair during menstrual cycles, which suggests that the endometriotic tissues have distinct mechanisms of fibrogenesis. During the development of en...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Circulation research
 
دوره 116 5 شماره
صفحات -
تاریخ انتشار 2015