Vascular Smooth Muscle Cell Stiffness: A Novel Mechanism for the Increased Aortic Stiffness in Hypertension and Aging

Hypertension and aging are both recognized to increase aortic stiffness, but the underlying mechanisms are not completely understood. Most prior studies have attributed increased aortic stiffness to mechanical changes within the extracellular matrix proteins of the aortic wall. Alternatively, we hypothesize that a significant component of increased vascular stiffness in hypertension is also due to changes in the mechanical properties of vascular smooth muscle cells (VSMCs), and that the contribution of this mechanism is augmented during hypertensive aging. Accordingly, we studied aortic stiffness in young (16wks) and old (64wks) spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) wild-type controls. Systolic aortic pressure, measured by Millar micromanometer catheter, was significantly increased in the old compared to young SHR (191±8 mmHg vs 157±6 mmHg, p < 0.01), but not in WKY (old, 109±6 mmHg vs young, 102±6 mmHg). Excised aortic ring segments were subjected to physiological levels of mechanical stretch ex vivo, and the wall stress within these ring segments, as well as their tangential elastic moduli, were greater in SHR vs WKY (p < 0.05). VSMCs were isolated from the thoracic aorta, and the elastic stiffness of individual VSMCs was measured by an atomic force microscopy nano-indentation technique. Hypertension increased VSMC stiffness more, p < 0.05, in young SHR (26±4 kPa) compared to young WKY (14±2 kPa). Aging also increased VSMC stiffness, p < 0.05, in old versus young SHR. Importantly, the increase in VSMC stiffness in young SHR versus young WKY (92±15%) was less, p < 0.05, than that observed between old SHR versus old WKY (131±2%). Our findings that the mechanical properties of VSMCs are sensitive to hypertension, and also to aging, suggests this as a novel mechanism for increased aortic stiffness that occurs with hypertension and aging. (NIH 5R01HL102472-SFV and NIH PO1-HL-095486-GAM)