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MiRNA-132/212 encapsulated by adipose tissue-derived exosomes worsen atherosclerosis progression.
- Source :
-
Cardiovascular diabetology [Cardiovasc Diabetol] 2024 Sep 09; Vol. 23 (1), pp. 331. Date of Electronic Publication: 2024 Sep 09. - Publication Year :
- 2024
-
Abstract
- Background: Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes.<br />Methods: The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests.<br />Results: We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX.<br />Conclusion: These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis.<br /> (© 2024. The Author(s).)
- Subjects :
- Animals
Humans
Male
Mice
Aortic Diseases pathology
Aortic Diseases metabolism
Aortic Diseases genetics
Becaplermin pharmacology
Becaplermin metabolism
Cells, Cultured
Endothelial Cells metabolism
Endothelial Cells pathology
Endothelial Cells drug effects
Intra-Abdominal Fat metabolism
Intra-Abdominal Fat pathology
Mice, Knockout, ApoE
Obesity metabolism
Obesity pathology
Signal Transduction
Apoptosis drug effects
Atherosclerosis metabolism
Atherosclerosis pathology
Atherosclerosis genetics
Cell Movement drug effects
Cell Proliferation drug effects
Disease Models, Animal
Disease Progression
Exosomes metabolism
Exosomes pathology
Mice, Inbred C57BL
MicroRNAs metabolism
MicroRNAs genetics
Muscle, Smooth, Vascular pathology
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular drug effects
Myocytes, Smooth Muscle metabolism
Myocytes, Smooth Muscle pathology
Myocytes, Smooth Muscle drug effects
Plaque, Atherosclerotic
Subjects
Details
- Language :
- English
- ISSN :
- 1475-2840
- Volume :
- 23
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cardiovascular diabetology
- Publication Type :
- Academic Journal
- Accession number :
- 39252021
- Full Text :
- https://doi.org/10.1186/s12933-024-02404-x