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Role of Endothelial Potassium Channels in Vasodilation Under Normal and Dyslipidemic Condition

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thesis
posted on 01.11.2017, 00:00 by Sang Joon Ahn
Inwardly rectifying potassium (Kir) channels are known to maintain cellular membrane potential and are putatively sensitive to mechanical stimuli. Kir channels are expressed in various cell types including endothelial cells; however, their role in vascular physiology is not well understood. In this thesis, I provide several lines of evidence that endothelial Kir channels are essential for flow-induced vasodilation (FIV) through NO production: i) FIV was impaired in genetically deficient Kir2.1 mice, ii) endothelial cells isolated from Kir2.1 deficient mice showed the loss of flow-induced eNOS activation, iii) expression of endothelial-specific WT-Kir2.1 in Kir2.1 deficient endothelial cells recovered FIV and eNOS activation, iv) flow-induced NO production was reduced in Kir2.1 impaired mice, and v) mean blood pressure was elevated in Kir2.1 impaired mice due to an increase in peripheral vascular resistance. Additionally, my data suggest that Kir channels play a key role in receptor-mediated vasodilation through NO production: i) receptor-mediated vasodilation was impaired in genetically deficient Kir2.1 mice, ii) receptor-mediated NO production was impaired in Kir2.1 deficient endothelial cells, and iii) expression of WT-Kir2.1 channels in endothelial cells from Kir2.1 deficient mice showed the recovery of receptor-mediated NO production. Our laboratory previously showed that Kir channel activity was reduced by cholesterol binding; therefore, I tested the role of Kir channels in impaired FIV in dyslipidemia. My data suggest that the reduction of FIV in dyslipidemia was due to the loss of Kir channel activity. Additionally, I found that Kir channel deficiency exacerbated lesion formation in aortas of hypercholesterolemic mice.

History

Advisor

Levitan, Irena

Chair

Levitan, Irena

Department

Bioengineering

Degree Grantor

University of Illinois at Chicago

Degree Level

Doctoral

Committee Member

Eddington, David Lee, James Phillips, Shane Park, Gye Young

Submitted date

August 2017

Issue date

10/07/2017

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