Vascular calcification is recognized as an independent predictor of cardiovascular morbidity and mortality, particularly in subjects with chronic kidney disease (CKD). The incidence of CKD has dramatically increased in the past decades due to the obesity and diabetes epidemics. Although a number of causative and inhibitory factors for vascular calcification have been identified, the precise mechanism as well as an effective therapy for vascular calcification have not been established. In addition, the pathways by which dysregulation of lipid and mineral metabolism simultaneously occur in this particular population remain unclear.
Our current research focuses on understanding the molecular mechanism for the development of vascular calcification and to identify a novel target for treatment of CKD-dependent vascular diseases. To achieve these goals, we are currently conducting the following research projects:
1) Role of bile acid signaling through FXR in the regulation of atherosclerotic and medial vascular calcification.
2) Role of bile acid signaling through TGR5 in the regulation of atherosclerosis.
3) Molecular mechanisms by which stearate induces vascular calcification.
4) Identification of a pro-calcific molecule derived from endogenously-synthesized stearate.
To address these areas of emphasis, we have been using a wide variety of molecular and cell biology techniques, including genetically modified animal models using Cre-loxP and Tet-O systems.