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Catalpol ameliorates hyperglycemia-stimulated resistin through macrophage-derived exosomal miRNA-150-5p in diabetic
Chiu-Mei Lin1, Bao-Wei Wang2, Chun-Ming Pan2
1Department of Emergency Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taiwan; Faculty of Medicine, School of Medicine, Fu Jen Catholic University, Taiwan.
Abstract:
MicroRNA 150 (miR-150) and exosomal miR-150 are the circulating and potential cardiovascular therapeutic targets. The downregulation of macrophage-derived exosomal miR-150-5p and overexpression of resistin affect the diabetic pathogenesis. Catalpol, an iridoid glucoside, has anti-diabetic, cardiovascular protective, and anti-inflammatory effects. The aim of this study was to investigate the cardioprotective effects of catalpol due to enhanced macrophage-derived exosomal miR-150-5p under hyperglycemia stress in vitro and in vivo. Catalpol and macrophage-derived exosomal miR-150-5p were the treatments in these diabetic atherosclerotic models. Luciferase activity assay, immunohistochemistry, and immunofluorescent analyses were employed. The data revealed that hyperglycemic stress suppressed the exosomal miR-150-5p levels in high glucose (25 mM)-cultured mouse macrophages, however, increased their resistin levels. Treatment with catalpol, pretreated-catalpol-macrophage-derived exosomes augmented the levels of exosomal miR-150-5p in mouse macrophage cultures under hyperglycemic stress in vitro, ameliorated resistin presentation simultaneously. Treatment with pretreated-catalpol-macrophage-derived exosomes, catalpol (5 mg/kg), and exosomal miR-150-5p dominant considerably reduced the neointimal sizes by 37.6 %, 24.8 % and 39.7 %, respectively, after 14 days of balloon injury in vivo. Our novelty of findings indicate catalpol ameliorates resistin and neointimal hyperplasia formation under hyperglycemia stress by mediating the macrophage-derived exosomal miR-150-5p. Catalpol has cardioprotective effects to modulate the ell-to-cell communication in a hyperglycemic microenvironment.
Insights
Catalpol enhances microRNA 150 (miR-150) in exosomes derived from macrophages, protecting against diabetic cardiovascular damage. This compound reduces resistin and neointimal hyperplasia, offering a novel therapeutic approach for hyperglycemia-related conditions.
Area of Science:
- Biomedical Science
- Cardiovascular Research
- Molecular Biology
Background:
- MicroRNA 150 (miR-150) and its exosomal form are crucial circulating biomarkers and potential therapeutic targets for cardiovascular diseases.
- Diabetic pathogenesis is linked to reduced macrophage-derived exosomal miR-150-5p and increased resistin levels.
- Catalpol, an iridoid glucoside, exhibits anti-diabetic, cardiovascular protective, and anti-inflammatory properties.
Purpose of the Study:
- To investigate the cardioprotective effects of catalpol by enhancing macrophage-derived exosomal miR-150-5p under hyperglycemic conditions.
- To evaluate catalpol's impact on resistin levels and neointimal hyperplasia in diabetic atherosclerotic models.
- To elucidate the mechanism by which catalpol modulates cell-to-cell communication in a hyperglycemic microenvironment.
Main Methods:
- In vitro studies using high glucose-cultured mouse macrophages to assess exosomal miR-150-5p and resistin levels.
- In vivo studies involving diabetic atherosclerotic models subjected to balloon injury.
- Treatments included catalpol, catalpol-pretreated macrophage-derived exosomes, and dominant exosomal miR-150-5p.
- Luciferase activity assay, immunohistochemistry, and immunofluorescent analyses were employed.
Main Results:
- Hyperglycemic stress decreased exosomal miR-150-5p and increased resistin in macrophages.
- Catalpol and catalpol-pretreated exosomes increased exosomal miR-150-5p and reduced resistin in vitro.
- Treatments significantly reduced neointimal sizes in vivo: catalpol (24.8%), catalpol-pretreated exosomes (37.6%), and exosomal miR-150-5p (39.7%) after 14 days.
Conclusions:
- Catalpol ameliorates resistin and neointimal hyperplasia formation under hyperglycemia by mediating macrophage-derived exosomal miR-150-5p.
- Catalpol demonstrates cardioprotective effects through modulation of cell-to-cell communication in hyperglycemic conditions.
- This study highlights catalpol as a potential therapeutic agent for diabetic cardiovascular complications by targeting exosomal miR-150-5p.
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