Attenuated Superoxide Dismutase 2 Activity Induces Atherosclerotic Plaque Instability During Aging in Hyperlipidemic Mice

Journal of the American Heart Association
Aleksandr E VendrovMarschall S Runge

Abstract

Atherosclerosis progression during aging culminates in the development of vulnerable plaques, which may increase the risk of cardiovascular events. Increased generation and/or decreased scavenging of reactive oxygen species in the vascular wall are major contributors to atherogenesis. We previously showed that superoxide dismutase 2 deficiency increased vascular oxidative stress and reduced aortic compliance in aged wild-type mice and that young Apoe-/-/Sod2+/- had increased mitochondrial DNA damage and atherosclerosis versus young Apoe-/- mice. Here we investigated the effects of superoxide dismutase 2 deficiency on atherosclerosis progression and plaque morphology in middle-aged Apoe-/- mice. Compared with Apoe-/-, middle-aged Apoe-/-/Sod2+/- mice had increased vascular wall reactive oxygen species (P<0.05) and higher atherosclerotic lesion area (P<0.001). The atherosclerotic plaques in middle-aged Apoe-/-/Sod2+/- mice had an increased necrotic core with higher inflammatory cell infiltration, a thinned fibrous cap with depleted smooth muscle content, and intraplaque hemorrhage. In addition, the plaque shoulder area had higher levels of calpain-2, caspase-3, and matrix metalloproteinase-2 in intimal smooth muscle cells and dep...Continue Reading

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Citations

Dec 11, 2019·Circulation Research·Daniel J TyrrellDaniel R Goldstein
Sep 13, 2020·Nature Reviews. Cardiology·Daniel J Tyrrell, Daniel R Goldstein
Mar 21, 2018·Frontiers in Cardiovascular Medicine·Goro KatsuumiTohru Minamino
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Jul 8, 2020·Biology·Anastasia V PoznyakAlexander N Orekhov
Feb 11, 2021·Journal of Personalized Medicine·Jolien FledderusGuido Krenning
Dec 29, 2019·Molecular Aspects of Medicine·Helena C F Oliveira, Anibal E Vercesi
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May 4, 2021·Brain Communications·Vanessa Di CataldoEmmanuelle Canet-Soulas
Jun 18, 2021·Advanced Drug Delivery Reviews·Alexandros Marios SofiasTwan Lammers
Dec 7, 2021·Frontiers in Physiology·Tianlong LiuJingzhou Chen

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Datasets Mentioned

BETA
AG024282

Methods Mentioned

BETA
ISS
Assay
transfection
zymography
polarized microscopy
ubiquitination
pharmacotherapy

Software Mentioned

Adobe Photoshop
JMP Pro
NIH ImageJ
Prism
MitoTEMPO

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