Mechanosensing in the Development of Hypertension From ESH 2016 Plenary Session Jay D Humphrey PhD Yale University New Haven Connecticut USA Overview Arterial stiffness AS is an independent predictor of allcause and cardiovascular CV mortality in hypertension ID: 1033380
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1. Contribution of Dysfunctional Mechanosensing in the Development of HypertensionFrom ESH 2016 | Plenary Session:Jay D. Humphrey, PhDYale University, New Haven, Connecticut, USA
2. OverviewArterial stiffness (AS) is an independent predictor of all-cause and cardiovascular (CV) mortality in hypertensionResearch is elucidating mechanisms of AS Humphrey and colleagues investigating roles of mechanosensing and mechanoregulation in development and maintenance of ASMechanosensing and mechanoregulation are processes through which the cell responds to stress to maintain a homeostatic state. The fibroblast responds to stress through remodeling of the extracellular matrix (ECM), including expression of integrins.
3. OverviewIn mouse model of AS, cells work to maintain constant level of AS, causing arterial wall thickening and ultimately increased blood pressure and pulse wave velocity; wave reflections return earlier in cardiac cycle, pressures in central region are augmentedWork in animal models has shown a positive feedback loopIn models of induced hypertension, even in the presence of normal mechanoadaptations, increased blood pressure causes compensatory arterial wall thickening, thereby increasing structural stiffness. Inflammation maintains wall thickness. This suggests dysfunctional mechanosensing and mechanoregulation of the ECM
4. OverviewMechanical homeostasis is sought at the subcellular level, in cytoskeletal filaments and fibroblast adhesions; at the cell, cell-cell, and cell-matrix level; and at the tissue and organ level, with altered geometry, structure, and properties and many pathophysiologic responsesAmong responses to mechanical stress are increased Angiotensin II production, increased monocyte chemoattractant protein-1 production (driving inflammation), changes in contractile protein expression and integrins and their clustering
5. OverviewAngiotensin II infusion in mouse model caused adventitial and medial thickeningmedia contains elastin fibers that store the energy needed to recoil the vessel during systole, diastole, and normal flowadventitia becomes protective sheath for smooth muscle cells and elastin fibrin during media stress from increased blood pressureAdventitia bears most stress, which may explain the fibrotic response
6. Contribution of Dysfunctional Mechanosensing in the Development of HypertensionFrom ESH 2016 | Plenary Session:Jay D. Humphrey, PhDYale University, New Haven, Connecticut, USA