Impairment of Flow-Sensitive Inwardly Rectifying K⁺ Channels via Disruption of Glycocalyx Mediates Obesity-Induced Endothelial Dysfunction.

ABSTRACT:

Objective

To determine if endothelial dysfunction in a mouse model of diet-induced obesity and in obese humans is mediated by the suppression of endothelial Kir (inwardly rectifying K⁺) channels. Approach and Results: Endothelial dysfunction, observed as reduced dilations to flow, occurred after feeding mice a high-fat, Western diet for 8 weeks. The functional downregulation of endothelial Kir2.1 using dominant-negative Kir2.1 construct resulted in substantial reductions in the response to flow in mesenteric arteries of lean mice, whereas no effect was observed in arteries of obese mice. Overexpressing wild-type-Kir2.1 in endothelium of arteries from obese mice resulted in full recovery of the flow response. Exposing freshly isolated endothelial cells to fluid shear duri

SUBMITTER: Fancher IS 

PROVIDER: S-EPMC7503211 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature