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

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

  • Int J Mol Sci. 2023 Feb 14;24(4):3857. doi: 10.3390/ijms24043857.
Yutang Wang 1,  Dinh Tam Nguyen 1,  Jack Anesi 1,  Ahmed Alramahi 1,  Paul K Witting 2,  Zhonglin Chai 3,  Abdul Waheed Khan 3,  Jason Kelly 4,  Kate M Denton 5 6,  Jonathan Golledge 7 8
Affiliations

Affiliations

  • 1 Discipline of Life Science, Institute of Innovation, Science and Sustainability, Federation University Australia, Ballarat, VIC 3350, Australia.
  • 2 Molecular Biomedicine Theme, School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, The University of Sydney, Sydney, NSW 2006, Australia.
  • 3 Department of Diabetes, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
  • 4 Fiona Elsey Cancer Research Institute, Ballarat, VIC 3350, Australia.
  • 5 Department of Physiology, Monash University, Melbourne, VIC 3800, Australia.
  • 6 Cardiovascular Disease Program, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3800, Australia.
  • 7 Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia.
  • 8 Department of Vascular and Endovascular Surgery, The Townsville University Hospital, Townsville, QLD 4814, Australia.
PMID: 36835270 DOI: 10.3390/ijms24043857
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.

Keywords

atherosclerosis; cell migration; inflammation; moxonidine.

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