Hypertension and aging effects on vascular smooth muscle cell contribution to reconstituted aortic tissue elasticity

The cellular contribution to increased aortic stiffness associated with hypertension and aging is not fully understood. To study this potential role, a reconstituted aortic tissue model (vascular smooth muscle cells (VSMCs) in a collagen matrix) was developed. VSMCs isolated from thoracic aortic samples of 5-week and 18-week old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were passaged four times, and separately incubated in collagen around cylindrical mandrels for two days. The resulting tissue rings were subjected to repeated 10% strain steps. The ratio of the steady-state increase of uniaxial stress following the step compared to the 10% strain determined tissue elasticity. This was measured for the intact reconstituted tissue; and following treatment with an actin cytoskeletal disrupter (cytochalasin D), which effectively removed the cellular contribution to tissue elasticity. The cellular contribution was found from the difference between these elasticities. Aging and hypertension sharply increased VSMC elasticities (mean ± SEM): 18-week old SHR (1.45 ± 0.17 kPa) showed a 6-fold difference compared to 5-week old SHR (0.24 ± 0.07 kPa), and a 4-fold difference compared to 18-week old WKY (0.33 ± 0.14 kPa). These data suggest that cellular contributions to aortic stiffness may increase with aging and hypertension.