Distinct Cell-ECM Interactions in Women’s Ascending Aorta

Aortic aneurysms arising in the ascending aorta carry a high rate of mortality and morbidity and place patients at risk of aortic dissection. Several studies indicate that more men are affected with ascending thoracic aortic aneurysm (ATAA) than women, yet more women die of complications related to ATAA than men. ATAA are broadly characterized by smooth muscle cell (SMC) dysfunction and extracellular matrix (ECM) degradation. The goal of this project is to identify sex-differentiating factors in SMCs from men and women with ATAA, focusing on SMC interactions with ECM (collagen). Aortic specimens were obtained from ATAA resected during aortic replacement and from non-aneurysmal (NA) aorta (aortic punches) collected during bypass surgeries at the Brigham and Women’s Hospital. Aortic SMCs were derived from NA and ATAA specimens and propagated in presence or absence of a collagen coating to study SMC-collagen interactions. The effect of collagen was assessed by measuring SMCs contraction. In absence of collagen, aortic SMCs from women and men specimens exhibited similar contraction levels. However, culture of SMCs on collagen prior to the assay reduced the contraction intensity for SMCs from women specimens only but did not affect the contraction of SMCs from men specimens. These differences were observed in both the ATAA and NA groups. SMCs from ATAA were less contractile when compared to SMCs from NA aortic specimens but there was no difference in contraction between the sexes within the NA or ATAA group. These results demonstrate that aortic SMCs from women specimens have an inherently distinct response to collagen substrate when compared to aortic SMCs from men specimens. Future experiments are needed to determine if this observation plays a role in the increased aortic complications in women with ATAA vs. men.