Interference With Akt Signaling Protects Against Myocardial Infarction And Death By Limiting The Consequences Of Oxidative Stress

Title

Interference With Akt Signaling Protects Against Myocardial Infarction And Death By Limiting The Consequences Of Oxidative Stress

Creator

Kerr B A; Ma L N; West X Z; Ding L; Malinin N L; Weber M E; Tischenko M; Goc A; Somanath P R; Penn M S; Podrez E A; Byzova T V

Publisher

Science Signaling

Date

2013
2013-08

Description

The intricacy of multiple feedback loops in the pathways downstream of Akt allows this kinase to control multiple cellular processes in the cardiovascular system and precludes inferring consequences of its activation in specific pathological conditions. Akt1, the major Akt isoform in the heart and vasculature, has a protective role in the endothelium during atherosclerosis. However, Akt1 activation may also have detrimental consequences in the cardiovascular system. Mice lacking both the high-density lipoprotein receptor SR-BI (scavenger receptor class B type I) and ApoE (apolipoprotein E), which promotes clearance of remnant lipoproteins, are a model of severe dyslipidemia and spontaneous myocardial infarction. We found that Akt1 was activated in these mice, and this activation correlated with cardiac dysfunction, hypertrophy, and fibrosis; increased infarct area; cholesterol accumulation in macrophages and atherosclerosis; and reduced life span. Akt1 activation was associated with inflammation, oxidative stress, accumulation of oxidized lipids, and increased abundance of CD36, a major sensor of oxidative stress, and these events created a positive feedback loop that exacerbated the consequences of oxidative stress. Genetic deletion of Akt1 in this mouse model resulted in decreased mortality, alleviation of multiple complications of heart disease, and reduced occurrence of spontaneous myocardial infarction. Thus, interference with Akt1 signaling in vivo could be protective and improve survival under dyslipidemic conditions by reducing oxidative stress and responses to oxidized lipids.

Subject

adhesion molecule-1 expression; Biochemistry & Molecular Biology; cardiac dysfunction; Cell Biology; density-lipoprotein; extends life-span; foam cell-formation; nf-kappa-b; nitric-oxide; oxidized phospholipids; scavenger receptor cd36; sr-bi

Format

Journal Article or Conference Abstract Publication

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Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

12-12

Issue

287

Volume

6

Citation

Kerr B A; Ma L N; West X Z; Ding L; Malinin N L; Weber M E; Tischenko M; Goc A; Somanath P R; Penn M S; Podrez E A; Byzova T V, “Interference With Akt Signaling Protects Against Myocardial Infarction And Death By Limiting The Consequences Of Oxidative Stress,” NEOMED Bibliography Database, accessed September 27, 2021, https://neomed.omeka.net/items/show/10451.

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