PB0019 - Bambi-deficiency enhances adipose tissue browning, ameliorates dyslipidemia and confers protection against atherosclerosis

Background: BAMBI is a TGFβ superfamily transmembrane protein that is highly expressed in platelets and endothelial cells. We have previously shown that endothelial Bambi plays a key role in thrombus formation and stability via modulating the endothelium anticoagulant properties. Several members of the TGFβ superfamily play a role in atherosclerosis and/or adipose tissue function however the role of BAMBI is not fully understood.

Aims: To evaluate the role of BAMBI in atherosclerosis.

Methods: Bambi-/-Ldlr-/- and Bambi+/+Ldlr-/- mice were fed a high fat diet (HFD) and aortic plaques analysed by oil red-O staining or immunohistochemistry. Plasma cholesterol, triglyceride, thrombin-antithrombin levels were determined. Adipose tissues from chow-fed Bambi-/- and Bambi+/+ mice were analysed by histology, qPCR and western-blotting.

Results: Bambi deficiency significantly reduced the formation of atherosclerotic lesions in the descending aortas but not in aortic arches. Analysis of the plaque composition in aortic arches revealed no differences in the macrophage content or anticoagulant phenotype of the endothelium but an increase in collagen content in Bambi-/-Ldlr-/- plaques. Plasma cholesterol and triglyceride levels were also significantly lower in Bambi-/-Ldlr-/- mice. A significant reduction of body weight was observed in Bambi-/- mice compared to Bambi+/+ mice fed a normal chow diet, and in Bambi-/-Ldlr-/- males fed a HFD. No difference in adipose tissue weight was observed in Bambi-/- mice compared to Bambi+/+ mice but adipocyte size was significantly reduced in white adipose tissues (WAT) with increased expression of uncoupling protein 1.

Conclusion(s): So far, our results suggest Bambi deficiency protects against atherosclerosis via modulation of lipid metabolism and favoring a stable plaque but not its influence on coagulation. We also highlight a role for BAMBI in adipose tissue although additional studies under HFD are warranted to confirm the browning phenotype of the subcutaneous WAT.