Jifeng Zhang, PhD
Lemin Zheng, PhD
Wei Li, MD
JI Program: Cardiovascular Medicine
Project Status: Active/Ongoing
Aortic aneurysm and dissection (AAD) is a high-risk cardiovascular disease with no approved drug currently available for treatment. Once ruptured, the mortality rate is as high as 65%-85%. It creates an urgent need to identify novel targets for developing drug-based therapeutic strategies. Using the untargeted metabolomic analysis from 20 AAD patients and 20 control samples, we found that succinate was the most upregulated metabolite in AAD patients, which was confirmed in the validation cohort (1,665 patients) by targeted metabolomic assay. In addition, we showed that succinate administration exacerbated Angiotensin II-induced AAD in the mouse model. We propose to identify novel metabolic markers and pathways in AAD development through screening more patient samples with multi-omics approaches and data mining. Combining our unique clinical resources, data mining strategies, and well established murine AAD models, this project aims to determine the key metabolites and molecular markers by multiomics approaches and data mining and to demonstrate that succinate supplementation aggravates AAD in the more clinically relevant BAPN/Ang II-induced AAD murine models. This work will provide a premier resource that will be shared with the research community and set the foundation for developing novel diagnoses and therapies for AAD and other related cardiovascular diseases.