Metformin regulates oxLDL-facilitated endothelial dysfunction by modulation of SIRT1 through repressing LOX-1-modulated oxidative signaling

Ching-Hsia Hung; Shih-Hung Chan; Pei-Ming Chu; Huei-Chen Lin; Kun-Ling Tsai

doi:10.18632/oncotarget.7387

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Research Papers: Gerotarget (Focus on Aging):

Metformin regulates oxLDL-facilitated endothelial dysfunction by modulation of SIRT1 through repressing LOX-1-modulated oxidative signaling

Ching-Hsia Hung _, Shih-Hung Chan, Pei-Ming Chu, Huei-Chen Lin and Kun-Ling Tsai

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Oncotarget. 2016; 7:10773-10787. https://doi.org/10.18632/oncotarget.7387

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Abstract

Ching-Hsia Hung1,2, Shih-Hung Chan3, Pei-Ming Chu4, Huei-Chen Lin2,5 and Kun-Ling Tsai1

1 Department of Physical Therapy, College of Medicine, National Cheng Kung University,Tainan, Taiwan

2 Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan

3 Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

4 Department of Anatomy, School of Medicine, China Medical University, Taichung, Taiwan

5 Department of Physical Therapy, Shu-Zen Junior College of Medicine and Management, Taiwan

Correspondence to:

Kun-Ling Tsai, email:

Keywords: metformin, endothelial dysfunction, oxLDL, SIRT1, Gerotarget

Received: January 02, 2016 Accepted: January 31, 2016 Published: February 14, 2016

Abstract

It is suggested that oxLDL is decisive in the initiation and development of atherosclerotic injuries. The up-regulation of oxidative stress and the generation of ROS act as key modulators in developing pro-atherosclerotic and anti-atherosclerotic processes in the human endothelial wall. In this present study, we confirmed that metformin enhanced SIRT1 and AMPK expression in human umbilical vein endothelial cells (HUVECs). Metformin also inhibited oxLDL-increased LOX-1 expression and oxLDL-collapsed AKT/eNOS levels. However, silencing SIRT1 and AMPK diminished the protective function of metformin against oxidative injuries. These results provide a new insight regarding the possible molecular mechanisms of metformin.

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Research Papers: Gerotarget (Focus on Aging):

Metformin regulates oxLDL-facilitated endothelial dysfunction by modulation of SIRT1 through repressing LOX-1-modulated oxidative signaling

Abstract