Modulation of mitochondrial structure and dynamics: a novel therapeutic strategy for prevention of restenosis

Research output: Contribution to conferencePoster

Abstract

Incomplete recovery of a functional endothelium following coronary stenting is associated with increased risk of restenosis and thrombosis. Pharmacological modulation of mitochondrial dynamics may retard restenosis via inhibition of smooth muscle proliferation; however the effects of such an approach on endothelial cell function remain unclear. With this in mind, the influence of the inhibitor of mitochondrial division, Mdivi-1 (0.1-10 µM), on endothelial cell mitochondria, cell proliferation and migration was assessed in vitro. Compared to control, Mdivi-1 (1 or 10 µM, 48 hr) significantly reduced fragmentation of the mitochondrial population (number of mitochondria relative to total mitochondrial area) within cultured endothelial cells, consistent with reduced mitochondrial fission. Similarly, Mdivi-1 reduced the fraction of motile mitochondria (66.0 ± 3.61% of mitochondria in control cells were motile vs 30.5 ± 2.87% in cells treated with 10 µM Mdivi-1; P<0.01). Mdivi-1 (10 µM) decreased endothelial cell migration by 40.9 ± 13.9%, as measured by movement of confluent cells into an adjacent cell-free “wound”. Mdivi-1 (10 µM) also inhibited cell proliferation over a 48 hr period, as measured by uptake of the DNA-binding chromophore bromodeoxyuridine by 80.1 ± 1.5% and 101.2 ± 8.78% in both normal and hyperglycaemic cell media (30.5 mM glucose vs 5.5 mM glucose in “normo-glycaemia”) respectively. These results suggest that mitochondria play an important role in the regulation of endothelial cell proliferation and migration. These findings may have important implications for the development of vascular disease therapeutics that rely on modulation of mitochondria.
Original languageEnglish
Publication statusPublished - 15 Oct 2017
Event12th International Congress on Innovations in Coronary Artery Disease: From Prevention to Intervention - Venice, Italy
Duration: 15 Oct 201717 Oct 2017
https://www.iccadcongress.com/

Conference

Conference12th International Congress on Innovations in Coronary Artery Disease
CountryItaly
CityVenice
Period15/10/1717/10/17
Internet address

Keywords

  • endothelium
  • coronary stenting
  • endothelial cell function
  • mitochondrial structure

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