| First Author | Aziz Q | Year | 2020 |
| Journal | J Mol Med (Berl) | Volume | 98 |
| Issue | 8 | Pages | 1149-1160 |
| PubMed ID | 32632751 | Mgi Jnum | J:307720 |
| Mgi Id | MGI:6724419 | Doi | 10.1007/s00109-020-01946-3 |
| Citation | Aziz Q, et al. (2020) Vascular KATP channels protect from cardiac dysfunction and preserve cardiac metabolism during endotoxemia. J Mol Med (Berl) 98(8):1149-1160 |
| abstractText | KATP channels in the vasculature composed of Kir6.1 regulate vascular tone and may contribute to the pathogenesis of endotoxemia. We used mice with cell-specific deletion of Kir6.1 in smooth muscle (smKO) and endothelium (eKO) to investigate this question. We found that smKO mice had a significant survival disadvantage compared with their littermate controls when treated with a sub-lethal dose of lipopolysaccharide (LPS). All cohorts of mice became hypotensive following bacterial LPS administration; however, mean arterial pressure in WT mice recovered to normal levels, whereas smKO struggled to overcome LPS-induced hypotension. In vivo and ex vivo investigations revealed pronounced cardiac dysfunction in LPS-treated smKO, but not in eKO mice. Similar results were observed in a cecal slurry injection model. Metabolomic profiling of hearts revealed significantly reduced levels of metabolites involved in redox/energetics, TCA cycle, lipid/fatty acid and amino acid metabolism. Vascular smooth muscle-localised KATP channels have a critical role in the response to systemic infection by normalising cardiac function and haemodynamics through metabolic homeostasis. KEY MESSAGES: * Mice lacking vascular KATP channels are more susceptible to death from infection. * Absence of smooth muscle KATP channels depresses cardiac function during infection. * Cardiac dysfunction is accompanied by profound changes in cellular metabolites. * Findings from this study suggest a protective role for vascular KATP channels in response to systemic infection. |
