Spontaneous experimental atherosclerosis in hypercholesterolemic mice advances with ageing and correlates with mitochondrial reactive oxygen species

Exp Gerontol. 2018 Aug:109:47-50. doi: 10.1016/j.exger.2017.02.010. Epub 2017 Feb 14.

Abstract

Ageing and atherosclerosis are associated with oxidative stress. Mitochondrial redox function declines with ageing. Here we tested whether ageing LDL receptor knockout mice (LDLr-/-) develop spontaneous atherosclerosis and whether mitochondrial reactive oxygen species (mtROS) correlate with atherosclerosis. Compared with young mice, aged LDLr-/- mice exhibited 20-fold larger aortic lesion size, although the plasma cholesterol levels did not vary between age groups. The lesion sizes increased exponentially from 3 to 24months of age (r=0.92, p=0.0001) and were correlated with mtROS across the age range (r=0.81, p=0.0001). Thus, LDLr-/- mice develop spontaneous diet-independent atherosclerosis, that advances exponentially with ageing. We propose that age related increases in mtROS contribute to accelerate atherosclerosis development in hypercholesterolemic mice.

Keywords: Atherosclerosis; Hypercholesterolemia; LDL receptor; Mitochondria; Reactive oxygen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging*
  • Animals
  • Atherosclerosis / etiology*
  • Hypercholesterolemia / complications*
  • Male
  • Mice
  • Mice, Knockout
  • Mitochondria / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Receptors, LDL / physiology

Substances

  • Reactive Oxygen Species
  • Receptors, LDL