Aortic & peripheral vascular disease
Untargeted metabolomics identifies succinate as a biomarker and therapeutic target in aortic aneurysm and dissection
An erratum to this article was published (Eur Heart J, 21 May 2023 ↗)
Authors' conclusion
Plasma succinate concentrations allow to distinguish patients with AAD from both healthy controls and patients with AMI or PE. Succinate concentrations are regulated by the p38α-CREB-OGDH axis in macrophages.
Study context
- Population
- Patients with aortic aneurysm and dissection (AAD); murine AAD modelsdiscovery 40
- Comparison
- AAD vs healthy controls, acute myocardial infarction (AMI) and PE
- Outcome
- Plasma succinate and mechanistic effects
Methodological detailsuntargeted metabolomics, discovery and validation cohorts, murine AAD models
- Untargeted metabolomics
- Discovery and validation cohorts
- Murine AAD models
Main finding
As reported in the abstract
- Succinate most upregulated metabolite in discovery cohort; confirmed in validation cohort
- Plasma succinate higher in AAD than healthy controls, AMI and PE
- Succinate administration aggravated angiotensin II-induced AAD and vascular inflammation in mice
- Oxoglutarate dehydrogenase (OGDH) knockdown reduced inflammatory factor expression in macrophages
- Conditional p38α deletion decreased CREB phosphorylation, OGDH expression and succinate concentrations
- Macrophage p38α deletion reduced angiotensin II-induced AAD
Original publication
Untargeted metabolomics identifies succinate as a biomarker and therapeutic target in aortic aneurysm and dissection. Eur Heart J. Published 17 September 2021. doi:10.
Summarised from the published abstract; every number is checked against it