Abstract 429: Thoracic Aortic Smooth Muscle Cell Phenotype and Contractility are Altered With Aging

Abstract

Background: Age-related changes in the thoracic aorta, including alterations in medial extracellular matrix (ECM) in terms of increased collagen and reduced medial cellularity, are associated with a loss of contractility in isolated smooth muscle cells (SMCs). SMCs can regulate both the passive ECM content and mechanical properties of the aorta. However, the age-dependent effects on cellular proliferation, migration, adhesion, and gene expression (phenotype) of aortic SMCs remains unknown. Accordingly, the goal of this study was to determine the age-dependent changes in these characteristics of aortic SMCs. Methods/Results: Primary cultures of SMCs were established from thoracic aortic explants harvested from 6 month (n=6) and 21 month old (n=6) C57BL/6 mice. Cellular proliferation (by Cyquant assay), migration (Boyden chamber), and adhesion (on a cell culture treated surface) were reduced in the SMCs from old mice compared to those from young mice. Expression of ECM remodeling genes, including ECM proteins, matrix metalloproteinases, and tissue inhibitors of MMPs, produced a distinct genotypic profile between old and young SMCs (Figure). Conclusions: Findings from this study demonstrated that thoracic aortic SMCs from old mice are phenotypically distinct compared to those from young mice. Further, the changes in gene expression with age are consistent with the ECM changes observed in the aorta. Future studies will be required to define the role of these age-related changes in aortic SMC phenotype in aortopathies.