Ming Wei1,2,3, Lu Gan4, Zheng Liu5, Li Liu6, Jin-Rui Chang1, Da-Chuan Yin2, Hui-Ling Cao2, Xing-Li Su7,8, Wanli W Smith9. 1. Department of Pharmacology, Xi'an Medical University, Xi'an, China. 2. Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Xi'an Medical University, Xi'an, China. 3. Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, China. 4. Department of Gynecology, Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. 5. College of Medical Laboratory Science, Guilin Medical University, Guilin, China. 6. Ultrasound Diagnostics Department, Shaanxi Provincial People's Hospital, Xi'an, China. 7. Department of Pharmacology, Xi'an Medical University, Xi'an, China, suxingli@xiyi.edu.cn. 8. Shaanxi Key Laboratory of Brain Disorders, Xi'an Medical University, Xi'an, China, suxingli@xiyi.edu.cn. 9. Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Abstract
INTRODUCTION: Vascular calcification (VC) is a complex, regulated process involved in many disease entities. So far, there are no treatments to reverse it. Exploring novel strategies to prevent VC is important and necessary for VC-related disease intervention. OBJECTIVE: In this study, we evaluated whether MOTS-c, a novel mitochondria-related 16-aa peptide, can reduce vitamin D3 and nicotine-induced VC in rats. METHODS: Vitamin D3 plus nicotine-treated rats were injected with MOTS-c at a dose of 5 mg/kg once a day for 4 weeks. Blood pressure, heart rate, and body weight were measured, and echocardiography was performed. The expression of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and the angiotensin II type 1 (AT-1) and endothelin B (ET-B) receptors was determined by Western blot analysis. RESULTS: Our results showed that MOTS-c treatment significantly attenuated VC. Furthermore, we found that the level of phosphorylated AMPK was increased and the expression levels of the AT-1 and ET-B receptors were decreased after MOTS-c treatment. CONCLUSIONS: Our findings provide evidence that MOTS-c may act as an inhibitor of VC by activating the AMPK signaling pathway and suppressing the expression of the AT-1 and ET-B receptors. The Author(s). Published by S. Karger AG, Basel.
INTRODUCTION:Vascular calcification (VC) is a complex, regulated process involved in many disease entities. So far, there are no treatments to reverse it. Exploring novel strategies to prevent VC is important and necessary for VC-related disease intervention. OBJECTIVE: In this study, we evaluated whether MOTS-c, a novel mitochondria-related 16-aa peptide, can reduce vitamin D3 and nicotine-induced VC in rats. METHODS:Vitamin D3 plus nicotine-treated rats were injected with MOTS-c at a dose of 5 mg/kg once a day for 4 weeks. Blood pressure, heart rate, and body weight were measured, and echocardiography was performed. The expression of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and the angiotensin II type 1 (AT-1) and endothelin B (ET-B) receptors was determined by Western blot analysis. RESULTS: Our results showed that MOTS-c treatment significantly attenuated VC. Furthermore, we found that the level of phosphorylated AMPK was increased and the expression levels of the AT-1 and ET-B receptors were decreased after MOTS-c treatment. CONCLUSIONS: Our findings provide evidence that MOTS-c may act as an inhibitor of VC by activating the AMPK signaling pathway and suppressing the expression of the AT-1 and ET-B receptors. The Author(s). Published by S. Karger AG, Basel.
Entities:
Keywords:
Adenosine monophosphate-activated protein kinase; Angiotensin II type 1; Endothelin B; MOTS-c; Rat model of vascular calcification
Authors: Cédric H G Neutel; Jhana O Hendrickx; Wim Martinet; Guido R Y De Meyer; Pieter-Jan Guns Journal: Int J Mol Sci Date: 2020-11-25 Impact factor: 5.923
Authors: Joseph C Reynolds; Rochelle W Lai; Jonathan S T Woodhead; James H Joly; Cameron J Mitchell; David Cameron-Smith; Ryan Lu; Pinchas Cohen; Nicholas A Graham; Bérénice A Benayoun; Troy L Merry; Changhan Lee Journal: Nat Commun Date: 2021-01-20 Impact factor: 14.919