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

Arteriosclerosis, Thrombosis, and Vascular Biology
Ibra S FancherIrena Levitan

Abstract

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 during patch-clamp electrophysiology revealed that the flow-sensitivity of Kir was virtually abolished in cells from obese mice. Atomic force microscopy revealed that the endothelial glycocalyx was stiffer and the thickness of the glycocalyx layer reduced in arteries from obese mice. We also identified that the length of the glycocalyx is critical to the flow-activation of Kir. Overexpressing Kir2.1 in endothelium of arteries from obese mice restored flow- and heparanase-sens...Continue Reading

References

May 31, 2002·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·I L WilliamsM T Kearney
Oct 7, 2004·Biophysical Journal·Victor G RomanenkoIrena Levitan
Apr 6, 2006·Journal of Internal Medicine·J M Tarbell, M Y Pahakis
Jan 27, 2007·Pflügers Archiv : European journal of physiology·Sietze ReitsmaMirjam G A oude Egbrink
Dec 8, 2007·The Journal of Physiology·Pamela D SmithDonald G Welsh
Feb 1, 2008·Inflammopharmacology·J N SharmaS S Parvathy
Jun 24, 2008·Pathophysiology : the Official Journal of the International Society for Pathophysiology·Phoebe A StapletonJefferson C Frisbee
Jun 9, 2009·Free Radical Biology & Medicine·Robert KumagaiGhassan S Kassab
Jul 16, 2010·Medicine and Science in Sports and Exercise·Sabeur TouatiPascal Laurant
Oct 1, 2010·Journal of Cardiovascular Pharmacology·David X Zhang, David D Gutterman
Jul 30, 2011·Biochimica Et Biophysica Acta·Dev K SinghIrena Levitan
Mar 7, 2013·Journal of Visualized Experiments : JoVE·Graham Marsh, Richard E Waugh
Sep 11, 2013·The Journal of Biological Chemistry·Avia Rosenhouse-DantskerIrena Levitan
Sep 14, 2013·Journal of Clinical Pharmacology·Noboru Toda, Tomio Okamura
Nov 28, 2013·PloS One·Anne WiesingerPhilipp Kümpers
Apr 20, 2014·Physiological Reports·Bart J M EskensJurgen W G E Vanteeffelen
May 23, 2014·Current Vascular Pharmacology·Dolores PrietoAna Sánchez
Jun 29, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Anne R CreceliusFrank A Dinenno
Aug 27, 2014·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Ivana GrizeljShane A Phillips
Feb 4, 2016·The Journal of Physiology·Swapnil K SonkusareMark T Nelson
Feb 27, 2017·American Journal of Physiology. Heart and Circulatory Physiology·Austin T RobinsonShane A Phillips
Jun 2, 2017·Journal of Visualized Experiments : JoVE·Kyung Ae KoJun-Ichi Abe
Jul 13, 2017·Biophysical Journal·Anne Marie W BartoschJohn M Tarbell
Oct 14, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Elizabeth Le MasterIrena Levitan
Dec 7, 2018·The Journal of Physiology·Christopher M HearonFrank A Dinenno

❮ Previous
Next ❯

Citations

Mar 26, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Shigeo GodoHiroaki Shimokawa

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.