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Downregulation of circulating MOTS-c levels in patients with coronary endothelial dysfunction.
- Source :
-
International journal of cardiology [Int J Cardiol] 2018 Mar 01; Vol. 254, pp. 23-27. Date of Electronic Publication: 2017 Dec 06. - Publication Year :
- 2018
-
Abstract
- Background: MOTS-c is one of the newly identified mitochondrial-derived peptides which play a role in regulating metabolic homeostasis. The current study aimed to investigate whether circulating MOTS-c levels are also associated with endothelial dysfunction(ED) in patients without significant structural coronary lesions.<br />Methods: Forty patients undergoing coronary angiography and endothelial function testing for clinical indications of recurrent angina with no structural coronary lesions were included in the study. They were divided into two groups based on coronary blood flow response to intracoronary acetylcholine (ACh) as normal endothelial function (≥ 50% increase from baseline) or ED, (n=20 each). Aortic plasma samples were collected at the time of catheterization for analysis of circulating MOTS-c levels by ELISA. The effect of MOTS-c on vascular reactivity was assessed in organ chambers using aortic rings collected from rats and renal artery stenosis (RAS) mice.<br />Results: Baseline characteristics were similar between the two groups. MOTS-c plasma levels were lower in patients with ED compared with patients with normal endothelial function (p=0.007). Furthermore, plasma MOTS-c levels were positively correlated with microvascular (p=0.01) and epicardial (p=0.02) coronary endothelial function. Although MOTS-c did not have direct vasoactive effects, pretreating aortic rings from rats or RAS mice with MOTS-c (2μg/ml) improved vessel responsiveness to ACh compared with vessels without MOTS-c treatment.<br />Conclusion: Lower circulating endogenous MOTS-c levels in human subjects are associated with impaired coronary endothelial function. In rodents, MOTS-c improves endothelial function in vitro. Thus, MOTS-c represents a novel potential therapeutic target in patients with ED.<br /> (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Adult
Animals
Aorta, Thoracic drug effects
Aorta, Thoracic metabolism
Biomarkers blood
Coronary Artery Disease diagnostic imaging
Coronary Circulation drug effects
Coronary Vessels drug effects
Coronary Vessels physiopathology
Down-Regulation drug effects
Endothelium, Vascular drug effects
Endothelium, Vascular physiopathology
Female
Humans
Male
Mice
Mice, Inbred C57BL
Middle Aged
Mitochondrial Proteins pharmacology
Organ Culture Techniques
Rats
Rats, Wistar
Coronary Artery Disease blood
Coronary Circulation physiology
Coronary Vessels metabolism
Down-Regulation physiology
Endothelium, Vascular metabolism
Mitochondrial Proteins blood
Subjects
Details
- Language :
- English
- ISSN :
- 1874-1754
- Volume :
- 254
- Database :
- MEDLINE
- Journal :
- International journal of cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 29242099
- Full Text :
- https://doi.org/10.1016/j.ijcard.2017.12.001