Investigating control of perivascular adipose tissue differentiation during cardiovascular disease Title: Investigating control of perivascular adipose tissue differentiation during cardiovascular disease Authors: Katie Stieber1,2, Joshua Boucher3, and Lucy Liaw1,2 1. University of Maine, Orono, ME 2. Maine Medical Center Research Institute, Scarborough, ME 3. IDEXX, Westbrook, ME Introduction: Obesity and cardiovascular disease are prevalent global health problems that are tightly linked. To understand this interaction, we study perivascular adipose tissue (PVAT), which surrounds most vessels and exerts a paracrine effect on the underlying smooth muscle. We are particularly interested in the control of adipogenesis and adipose expansion. Our lab previously found that suppression of Rab27a in pre-adipocytes leads to decreased lipid accumulation in differentiated adipocytes, indicating that Rab27a has a regulatory role during adipogenesis. The focus of this study is to compare human perivascular and subcutaneous adipose tissue (SubQ) from two groups of surgical patients – one undergoing mitral valve repair (VR) and one undergoing coronary artery bypass grafting (CABG). We plan to evaluate the donor groups by prevalence of obesity and diabetes, and expression of thermogenic adipogenic markers and Rab27a. Hypothesis: We hypothesize that VR donors will have a lower BMI, be less likely to be diabetic, and will have adipose tissue that displays more thermogenic features and decreased Rab27a expression, indicating lower adipose differentiation and expansion. Additionally, we expect PVAT to be more thermogenic and have lower Rab27a expression than SubQ. Methods: Demographic information was recorded from each donor. PVAT was collected from donors undergoing VR or CABG surgeries. The pre-adipocytes were isolated from the tissue and expanded into primary cell populations. The pre-adipocytes were induced to differentiate into adipocytes, and the expression of the novel thermogenic marker GRP75 and Rab27a were assessed by immunoblot. Results: The average BMI was 26.53 for those undergoing VR and 31.70 for CABG surgeries. Of the VR donors, 0 out of 11 had diabetes while 5 out of 16 of CABG patients did. Rab27a expression was decreased in VR donors and PVAT as compared to CABG donors and SubQ tissue. GRP75 levels were equivalent between groups. Conclusions: Given the difference in obesity and diabetes prevalence, as well as Rab27a expression, there are clear physiological differences between VR and CABG donors. These differences support the use VR donors as a non-cardiovascular disease control in comparison to CABG donors, who have severe coronary artery disease. Moving forward, we will continue to examine molecular differences between donors, as well as strive to understand Rab27a’s mechanistic control of adipose differentiation. Acknowledgments: This work was supported by the University of Maine institutional training grant 1T32GM132006-01 from the National Institute of General Medical Sciences (PIs: L. Liaw and C. Henry) and R01 HL141149 (PI: L. Liaw).