title: Increased vascular smooth muscle cell stiffness: a novel mechanism for aortic stiffness in hypertension.
abstract: Increased vascular stiffness is fundamental to hypertension, and its complications, including atherosclerosis, suggest that therapy should also be directed at vascular stiffness, rather than just the regulation of peripheral vascular resistance. It is currently held that the underlying mechanisms of vascular stiffness in hypertension only involve the extracellular matrix and endothelium. We hypothesized that increased large-artery stiffness in hypertension is partly due to intrinsic mechanical properties of vascular smooth muscle cells. After confirming increased arterial pressure and aortic stiffness in spontaneously hypertensive rats, we found increased elastic stiffness of aortic smooth muscle cells of spontaneously hypertensive rats compared with Wistar-Kyoto normotensive controls using both an engineered aortic tissue model and atomic force microscopy nanoindentation. Additionally, we observed different temporal oscillations in the stiffness of vascular smooth muscle cells derived from hypertensive and control rats, suggesting that a dynamic component to cellular elastic stiffness is altered in hypertension. Treatment with inhibitors of vascular smooth muscle cell cytoskeletal proteins reduced vascular smooth muscle cell stiffness from hypertensive and control rats, suggesting their participation in the mechanism. This is the first study demonstrating that stiffness of individual vascular smooth muscle cells mediates vascular stiffness in hypertension, a novel concept, which may elucidate new therapies for hypertension and for vascular stiffness.
authors.affiliation: Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Newark, New Jersey;
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Sehgel
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Sun
authors.forename: Jerome P
authors.initials: JP
authors.lastname: Trzeciakowski
authors.forename: Zhongkui
authors.initials: Z
authors.lastname: Hong
authors.forename: William C
authors.initials: WC
authors.lastname: Hunter
authors.forename: Dorothy E
authors.initials: DE
authors.lastname: Vatner
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Meininger
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Vatner
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology; D062186:Arterial Pressure; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004195:Disease Models, Animal; D004548:Elasticity; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors; D059289:Vascular Stiffness; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D003598:Cytoskeletal Proteins; D014662:Vasoconstrictor Agents
keywords: atomic force microscopy; hypertension; pulse wave velocity; vascular smooth muscle; vascular stiffness