Circulating plasma factors contribute to age‐associated arterial stiffness

Abstract

Previous findings from our laboratory showed that age‐related increases in large elastic artery stiffness in mice are associated with remodeling of the extracellular matrix (ECM), as indicated by increased collagen I expression, and oxidative stress, as indicated by increased nitrotyrosine staining. Here we tested the hypothesis that circulating factors in plasma contribute to arterial oxidative stress, ECM remodeling and stiffening. Nitrotyrosine, collagen I and elastic modulus, a measure of intrinsic mechanical stiffness, were determined in aortic rings from young (6 mo, n=4) male C57 mice cultured for 72 hours in media containing 10% plasma from either young (Yplasma) or old (Oplasma) mice. Compared with Yplasma, aortic rings incubated in Oplasma demonstrated increased NT abundance (3.11 ± 0.50 vs. 1.00 ± 0.30 AU, p<0.05), collagen I (1.66 ± 0.18 vs. 1.00 ± 0.12 AU, p<0.05) and elastic modulus (2780 ± 570 vs. 1768 ± 188 kPa, p=0.05). These preliminary results are consistent with the hypothesis that unknown factors in the circulating plasma induce “aging‐like” oxidative stress, ECM remodeling featuring increases in collagen I, and stiffening of the aorta. Identifying these circulating factors may lead to additional therapeutic targets for the prevention and treatment of ageassociated large elastic artery stiffening and clinical cardiovascular diseases.Supported by NIH AG013038, AG000279, HL007822