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Moxonidine Increases Uptake of Oxidised Low-Density Lipoprotein in Cultured Vascular Smooth Muscle Cells and Inhibits Atherosclerosis in Apolipoprotein E-Deficient Mice.

Abstract
This study aimed to investigate the effect of the sympatholytic drug moxonidine on atherosclerosis. The effects of moxonidine on oxidised low-density lipoprotein (LDL) uptake, inflammatory gene expression and cellular migration were investigated in vitro in cultured vascular smooth muscle cells (VSMCs). The effect of moxonidine on atherosclerosis was measured by examining aortic arch Sudan IV staining and quantifying the intima-to-media ratio of the left common carotid artery in apolipoprotein E-deficient (ApoE-/-) mice infused with angiotensin II. The levels of circulating lipid hydroperoxides in mouse plasma were measured by ferrous oxidation-xylenol orange assay. Moxonidine administration increased oxidised LDL uptake by VSMCs via activation of α2 adrenoceptors. Moxonidine increased the expression of LDL receptors and the lipid efflux transporter ABCG1. Moxonidine inhibited mRNA expression of inflammatory genes and increased VSMC migration. Moxonidine administration to ApoE-/- mice (18 mg/kg/day) decreased atherosclerosis formation in the aortic arch and left common carotid artery, associated with increased plasma lipid hydroperoxide levels. In conclusion, moxonidine inhibited atherosclerosis in ApoE-/- mice, which was accompanied by an increase in oxidised LDL uptake by VSMCs, VSMC migration, ABCG1 expression in VSMCs and lipid hydroperoxide levels in the plasma.
AuthorsYutang Wang, Dinh Tam Nguyen, Jack Anesi, Ahmed Alramahi, Paul K Witting, Zhonglin Chai, Abdul Waheed Khan, Jason Kelly, Kate M Denton, Jonathan Golledge
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 24 Issue 4 (Feb 14 2023) ISSN: 1422-0067 [Electronic] Switzerland
PMID36835270 (Publication Type: Journal Article)
Chemical References
  • Apolipoproteins E
  • Lipid Peroxides
  • Lipoproteins, LDL
  • moxonidine
  • oxidized low density lipoprotein
  • Imidazoles
Topics
  • Animals
  • Mice
  • Apolipoproteins E (metabolism)
  • Atherosclerosis (metabolism)
  • Cell Proliferation
  • Cells, Cultured
  • Lipid Peroxides (metabolism)
  • Lipoproteins, LDL (metabolism)
  • Mice, Inbred C57BL
  • Muscle, Smooth, Vascular (drug effects, metabolism)
  • Myocytes, Smooth Muscle (metabolism)
  • Imidazoles (pharmacology)

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