1. Powered by Infomedica Infomedica Conference Coverage* of 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 * Infomedica is an independent medical education provider that produces medical information to healthcare professionals through conference coverage and online educational programs and activities. 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 Contribution of Dysfunctional Mechanosensing in the Development of Hypertension From ESH 2016 | Plenary Session: Jay D. Humphrey, PhD Yale University, New Haven, Connecticut, USA

2. 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 Powered by Infomedica Overview  Arterial stiffness (AS) is an independent predictor of all-cause and cardiovascular (CV) mortality in hypertension  Research is elucidating mechanisms of AS  Humphrey and colleagues investigating roles of mechanosensing and mechanoregulation in development and maintenance of AS  Mechanosensing 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. 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 Powered by Infomedica Overview  In 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 augmented  Work in animal models has shown a positive feedback loop – In 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. 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 Powered by Infomedica Overview  Mechanical 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 responses  Among 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. 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 Powered by Infomedica Overview  Angiotensin II infusion in mouse model caused adventitial and medial thickening – media contains elastin fibers that store the energy needed to recoil the vessel during systole, diastole, and normal flow – adventitia becomes protective sheath for smooth muscle cells and elastin fibrin during media stress from increased blood pressure – Adventitia bears most stress, which may explain the fibrotic response

6. Powered by Infomedica Infomedica Conference Coverage* of 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 * Infomedica is an independent medical education provider that produces medical information to healthcare professionals through conference coverage and online educational programs and activities. 26 th European Meeting on Hypertension and Cardiovascular Protection Paris (France), June 10-13, 2016 Contribution of Dysfunctional Mechanosensing in the Development of Hypertension From ESH 2016 | Plenary Session: Jay D. Humphrey, PhD Yale University, New Haven, Connecticut, USA