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"Stiffness and Adhesion of Vascular Smooth Muscle Cells: Novel Mechanisms for Increased Arterial Stiffness in Hypertension"

by
Nancy L. Sehgel
Biomedical Engineering Program
M.S. 2011, New Jersey Institute of Technology
B.S. 2008, Rutgers University
B.A. 2008, Rutgers University


Thesis Advisor: Stephen F. Vatner, M.D.
University Professor
Department of Cell Biology & Molecular Medicine

Wednesday, April 29, 2015
3:00 P.M., MSB H-609b


Abstract

Increased arterial stiffness is sine qua non in the development of systemic hypertension, as well as the natural aging process. It is currently held that the underlying mechanisms of vascular stiffness predominantly involve the extracellular matrix (ECM), endothelium, and inflammatory mechanisms. Alternatively, it was hypothesized that the intrinsic mechanical properties of vascular smooth muscle cells (VSMCs) also contribute to increased large-artery stiffness in hypertension, and these contributions are augmented when hypertension is superimposed onto aging. Specifically, we proposed that the stiffness and adhesive properties of VSMCs partially underlie the increases in vascular stiffness. In this investigation, the spontaneously hypertensive rat (SHR), and their normotensive controls, Wistar-Kyoto rats (WKY) were studied at two age groups: at a young adult age (16-weeks old) when hypertension is fully established, and at an older age (64-weeks-old), when the effects of hypertension are superimposed on aging. The results of these studies demonstrated that arterial pressure and vascular stiffness were increased in SHR, compared to WKY in young and old animals. Aortic morphology and ECM protein composition were evaluated to reveal that hypertension, but not aging, is accompanied by an increase in medial layer thickness without a significant increase in collagen and elastin. VSMCs were isolated from excised aortic tissue segments to assess their mechanical properties. VSMC stiffness was measured using two complimentary techniques: within a 3D-tissue engineered gel model and also by atomic force microscopy (AFM) nano-indentation of individual cells. Additionally, the adhesive properties of VSMCs were assessed by AFM. Collectively, these studies demonstrate that VSMC stiffness is increased in hypertension, and that aging exacerbates VSMC stiffness and adhesion increases in hypertension. This investigation is the first to demonstrate that stiffness and adhesive properties of individual VSMCs are altered in hypertension, novel concepts, which may lead to elucidation of new therapies for hypertension and for vascular stiffness.


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