Untargeted metabolomics identifies succinate as a biomarker and therapeutic target in aortic aneurysm and dissection.

ABSTRACT:

Aims

Aortic aneurysm and dissection (AAD) are high-risk cardiovascular diseases with no effective cure. Macrophages play an important role in the development of AAD. As succinate triggers inflammatory changes in macrophages, we investigated the significance of succinate in the pathogenesis of AAD and its clinical relevance.

Methods and results

We used untargeted metabolomics and mass spectrometry to determine plasma succinate concentrations in 40 and 1665 individuals of the discovery and validation cohorts, respectively. Three different murine AAD models were used to determine the role of succinate in AAD development. We further examined the role of oxoglutarate dehydrogenase (OGDH) and its transcription factor cyclic adenosine monophosphate-responsive element-binding protei

SUBMITTER: Cui H 

PROVIDER: S-EPMC11506060 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature