Increases in Vascular Smooth Muscle Stiffness with Aging

Abstract

It is generally assumed that the increased aortic stiffness during aging is due to changes in the extracellular matrix (ECM). Our hypothesis was that the mechanical properties of vascular smooth muscle cells (VSMCs) contribute to the increased vascular stiffness with aging. Young (YM, 6.4±0.1 yr) and old male (OM, 25±0.4 yr) monkeys (Macaca fascicularis) (n=7/group) were studied. The mechanical properties of the VSMCs were measured in vitro using a VSMC‐ECM interaction model. Using the reconstituted tissue model with cultured aortic VSMC embedded in collagen, the tissue force response was measured with a force transducer and strain by a micrometer. The total stiffness of the VSMC construct in OM was higher (46.7±6.1 kPa, p<0.01) vs that in YM (27.4±4.9 kPa). Then cytochalasin D (2 μM) was used to disrupt the actin cytoskeleton of VSMC and eliminate the “active” force induced by VSMC, leaving the ECM component. The stiffness of ECM was greater (p<0.05) in OM (36.1±4.9 kPa) than in YM (20.6±3.9 kPa), and VSMC stiffness calculated from the difference between the total and the ECM stiffness, was also significantly higher (p<0.01) in OM (10.5±1.2 kPa) vs YM (6.8±1.0 kPa). Therefore, aortic VSMCs from OMs not only produce higher active forces compared to YMs but also remodel collagen more extensively to produce a stiffer ECM, which contributes to increased vascular stiffness with aging.