Targeting the PDK/PDH axis modulates neutrophil and smooth muscle cell pathological responses and prevents abdominal aortic aneurysm formation.

Aims: Abdominal aortic aneurysm (AAA) is a life-threatening condition where inflammation plays a key role. Currently, AAA treatment relies exclusively on surgical interventions, and no guideline drug therapy to prevent aneurysm growth or rupture is available. Pharmacological reprogramming of immune cell metabolism, through the modulation of the pyruvate dehydrogenase kinase/pyruvate dehydrogenase (PDK/PDH) axis, has been identified as an attractive strategy to combat inflammation.

Corrigendum: Selective inhibition of soluble tumor necrosis factor signaling reduces abdominal aortic aneurysm progression.

[This corrects the article DOI: 10.3389/fcvm.2022.

G-Protein-Coupled Receptor 91-Dependent Signalling Does Not Influence Vascular Inflammation and Atherosclerosis in Hyperlipidaemic Mice.

The TCA cycle intermediate metabolite 'succinate' has been proposed as an inflammatory mediator, influencing autoimmunity and allergic reactions, through ligation to its sensing receptor SUCNR1/GPR91. Whether GPR91-mediated signalling influences the chronic inflammatory process of atherosclerosis has never been investigated. The examination of publicly available datasets revealed that the gene is expressed in human atherosclerotic plaques, especially in vascular smooth muscle cells.

Selective inhibition of soluble tumor necrosis factor signaling reduces abdominal aortic aneurysm progression.

Background: Tumor necrosis factor (TNF) is pathologically elevated in human abdominal aortic aneurysms (AAA). Non-selective TNF inhibition-based therapeutics are approved for human use but have been linked to several side effects. Compounds that target the proinflammatory soluble form of TNF (solTNF) but preserve the immunomodulatory capabilities of the transmembrane form of TNF (tmTNF) may prevent these side effects.