Abstract 387: Age Associated B Cells Are Abundant In Perivascular Adipose Tissue In The Aortic Arch Region And Positively Associate With Atherosclerosis In Mice

Abstract

Background: Atherosclerosis development in the aorta is region specific with the aortic arch region more prone to disease development than descending thoracic and abdominal aorta. Perivascular adipose tissue (PVAT) directly associates with the aorta, harbors high numbers of B cells, and regulates atherosclerosis development. Age-Associated B cells (ABCs: CD19 + CD11c + ) have recently been reported as a new subset of B cells with unique cell surface and transcriptional signatures. ABCs have been reported to be elevated in autoimmune diseases, where in, these cells have characteristics of auto-antibody producing memory B cells. However, the impact of ABCs in the PVAT near aortic arch and with atherosclerosis progression during aging has not be studied. Methods and Results: To study ABCs in atherosclerosis setting, we used 50- and 100- week old chow diet fed, ApoE KO mice. Flow cytometric analysis showed that there was no difference in frequency of total B cells in the PVAT near the aortic arch region between 50- and 100- week old mice. However, the frequency of ABCs was significantly higher in aortic arch PVAT in 100-week-old mice compared to 50-week-old mice. Additionally, these ABCs in aortic arch PVAT are CD44 + (activation marker) and most ABCs were actively proliferating cells (Ki67 + ), as compared to other CD11c - B cells in 100-week-old ApoE KO mice. Lesion area was measured following Sudan-IV enface staining of aorta and 100-week-old mice developed significantly more disease than the 50-week-old mice. Interestingly, we observed a significant correlation of atherosclerosis disease in aortic arch region with the frequency of ABCs in PVAT near aortic arch (p=0.001, R 2 =0.69). Conclusion: Results provide the first evidence that ABCs in the aortic arch PVAT are highly active and the percentage of these ABCs strongly associates with advanced atherosclerosis disease in aged animals.