Leonurine Attenuates Myocardial Fibrosis Through Upregulation of miR-29a-3p in Mice Post-myocardial Infarction

Myocardial fibrosis (MF) is a pathological process that accelerates cardiac remodeling in myocardial infarction (MI), and miR-29 has become one of the foci of research into MF. As an alkaloid extracted from Herba leonuri, leonurine (LE) has been found to be an effective natural active ingredient for...

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Veröffentlicht in:Journal of cardiovascular pharmacology Jg. 77; H. 2; S. 189
Hauptverfasser: Wang, Ruiyu, Peng, Linqian, Lv, Dingyi, Shang, Feifei, Yan, Jianghong, Li, Guoxing, Li, Dan, Ouyang, Jing, Yang, Jiadan
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.02.2021
Schlagworte:
Angiotensin II - pharmacology
Animals
Cell Movement - drug effects
Cell Proliferation - drug effects
Cells, Cultured
Collagen - metabolism
Disease Models, Animal
Fibroblasts - drug effects
Fibroblasts - metabolism
Fibroblasts - pathology
Fibrosis
Gallic Acid - analogs & derivatives
Gallic Acid - pharmacology
Male
Mice
Mice, Inbred C57BL
MicroRNAs - genetics
MicroRNAs - metabolism
Myocardial Infarction - drug therapy
Myocardial Infarction - genetics
Myocardial Infarction - metabolism
Myocardial Infarction - physiopathology
Myocardium - metabolism
Myocardium - pathology
Transforming Growth Factor beta - metabolism
Up-Regulation
Ventricular Function, Left - drug effects
Ventricular Remodeling - drug effects
ISSN:1533-4023, 1533-4023
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Zusammenfassung:Myocardial fibrosis (MF) is a pathological process that accelerates cardiac remodeling in myocardial infarction (MI), and miR-29 has become one of the foci of research into MF. As an alkaloid extracted from Herba leonuri, leonurine (LE) has been found to be an effective natural active ingredient for inhibiting fibrosis in many preclinical experiments. However, whether LE protects against MF after MI through modifying miR-29 remains unclear. The present study aimed to investigate the therapeutic effects of LE on MF, and to elucidate the underlying mechanisms involved. A mouse model of MI was established, followed by administration of LE for 4 weeks. We found that LE effectively improved cardiac function, and attenuated fibrosis and cardiac remodeling in mice post-MI. In vitro, LE simultaneously inhibited proliferation and migration of neonatal mouse cardiac fibroblasts (CFs) exposed to angiotensin II (Ang II), and the activation of collagen synthesis and myofibroblast generation was markedly suppressed by LE. Notably, we found that all mature miR-29 family members were downregulated in the myocardial tissues of mice post-MI, whereas LE significantly upregulated miR-29a-3p expression, and such upregulation was also detected in LE-treated CFs under Ang II stimulation. Knockdown of miR-29a-3p by a specific miRNA inhibitor upregulated the protein levels of TGF-β, collagen III, and collagen I in CFs, and completely reversed the antifibrotic effects of LE on CFs. Our study suggests that LE exerts cardioprotective effects against MF, possibly through the upregulation of miR-29a-3p.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1533-4023
1533-4023
DOI:10.1097/FJC.0000000000000957