Novel indolic AMPK modulators induce vasodilatation through activation of the AMPK-eNOS-NO pathway.

ABSTRACT: Endothelial adenosine monophosphate-activated protein kinase (AMPK) plays a critical role in the regulation of vascular tone through stimulating nitric oxide (NO) release in endothelial cells. Since obesity leads to endothelial dysfunction and AMPK dysregulation, AMPK activation might be an important strategy to restore vascular function in cardiometabolic alterations. Here, we report the identification of a novel AMPK modulator, the indolic derivative IND6, which shows affinity for AMPKα1β1γ1, the primary AMPK isoform in human EA.Hy926 endothelial cells. IND6 shows inhibitory action of the enzymatic activity in vitro, but increases the levels of p-Thr¹⁷⁴AMPK, p-Ser¹¹⁷⁷eNOS and p-Ser⁷⁹ACC in EA.Hy926. This paradoxical finding might be explained by the abili

SUBMITTER: Sanz-Gomez M 

PROVIDER: S-EPMC8913687 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature