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.

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.