Goo Taeg Oh (Korea, Republic of)
Ewha Womans University
Life science
My research interests have been in cardiovascular development and disease, immune and vascular cell network, angiogenesis, acetylosome, and mouse genomics. With my experiences and scientific achievements, I had served the Review Board of Expert Committee on Life Science and Welfare, National Science and Technology Council and President of Korean Society for Vascular Biology and Medicine. I have initiated the foundation of Ewha Laboratory Animal Genomic Center and developed novel transgenic and knockout mouse models of human disease such as atherosclerosis (CD137, Ninj1, Retnla, Oasl1), and Ogden syndrome (Naa10). With scientific knowledge and insight from immune and vascular cell network research, my new research will be extended to study on the cellular function and molecular mechanism in the immune system that mediates the heart-to-brain bidirectional interaction network. This will provide a new paradigm to develop the therapeutical strategy by elucidating the physiopathological cause of cardio-cerebrovascular diseases in myocardial infarction and stroke mouse models.

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 Conference Calendar

ENDOTHELIAL TKK1 DEFICIENCY REDUCES ENOS MRNA LEVELS, PROMOTING ENDOTHELIAL DYSFUNCTION AND ATHEROGENESIS

Session Name
0640 - Endothelial cell biology in atherosclerosis (ID 6)
Session Type
Workshop - Pathogenesis, vascular biology
Date
Tue, 24.05.2022
Session Time
15:45 - 17:15
Room
Anitschkow - Silver Plenary hall
Presenter
Lecture Time
16:25 - 16:35

Abstract

Background and Aims

Deprivation of optimal endothelial nitric oxide synthase (eNOS) expression under athero-prone conditions leads to endothelial dysfunction, however little is known about the protector of eNOS under diseased condition. The aim of this study is to identify the role of endothelial TKK1 as homeostatic regulator for vascular inflammatory disease like atherosclerosis.

Methods

The expression levels of human or murine TKK1 and eNOS were confirmed in the endothelium of aortas. Lesion formation with measurement of blood pressure and endothelial wall shear stress was evaluated in vascular or whole-body deficiency of Tkk1 in apolipoprotein e-deficient (Apoe-/-) mice. Atherosclerotic aortas or HUVECs were used for flow cytometry, analysis of inflammation-associated gene expression and various RNA sequencing (RNA-seq) for identifying mechanistic features.

Results

Human and murine TKK1 were localized to ECs in athero-prone sites and both Apoe-/-mice lacking Tkk1 throughout the body and specifically in ECs promoted plaque progression, an effect preceded by endothelial dysfunction and elevated leukocyte infiltration. Endothelial Tkk1 deletion or TKK knockdown caused an enhanced inflammatory response accompanied by decreased NO bioavailability, reflecting reduced eNOS expression under athero-prone conditions. Mechanistically, knockdown of PI3K/Akt signaling-dependent TKK expression in HUVECs decreased the NOS3 mRNA levels following up-regulation of the negative regulatory micro-RNA, miR-584 and induced Erk1/2 and NF-κB activation. Treatment of miR-584 mimetics on HUVECs decreased NOS3 mRNA stability, while miR-584 inhibitor reversed TKK knockdown effects.

Conclusions

TKK1 is a novel regulator for NOS3 mRNA expression under athero-prone conditions, and endothelial miR-584 antagonism could be a feasible therapeutic target mechanism for maintaining eNOS in inflammatory vascular disorders.

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