The Proatherogenic Effect of Chronic Nitric Oxide Synthesis Inhibition in ApoE-Null Mice Is Dependent on the Presence of PPARα
Joint Authors
Vechoropoulos, Michal
Ish-Shalom, Maya
Shaklai, Sigal
Sack, Jessica
Stern, Naftali
Tordjman, Karen M.
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-01-22
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
Inhibition of endothelial nitric oxide synthase (eNOS) accelerates atherosclerosis in ApoE-null mice by impairing the balance between angiotensin II (AII) and NO.
Our previous data suggested a role for PPARα in the deleterious effect of the renin-angiotensin system (RAS).
We tested the hypothesis that ApoE-null mice lacking PPARα (DKO mice) would be resistant to the proatherogenic effect of NOS inhibition.
DKO mice fed a Western diet were immune to the 23% worsening in aortic sinus plaque area seen in the ApoE-null animals under 12 weeks of NOS inhibition with a subpressor dose of L-NAME, P=0.002.
This was accompanied by a doubling of reactive oxygen species (ROS-) generating aortic NADPH oxidase activity (a target of AII, which paralleled Nox1 expression) and by a 10-fold excess of the proatherogenic iNOS, P<0.01.
L-NAME also caused a doubling of aortic renin and angiotensinogen mRNA level in the ApoE-null mice but not in the DKO, and it upregulated eNOS in the DKO mice only.
These data suggest that, in the ApoE-null mouse, PPARα contributes to the proatherogenic effect of unopposed RAS/AII action induced by L-NAME, an effect which is associated with Nox1 and iNOS induction, and is independent of blood pressure and serum lipids.
American Psychological Association (APA)
Vechoropoulos, Michal& Ish-Shalom, Maya& Shaklai, Sigal& Sack, Jessica& Stern, Naftali& Tordjman, Karen M.. 2014. The Proatherogenic Effect of Chronic Nitric Oxide Synthesis Inhibition in ApoE-Null Mice Is Dependent on the Presence of PPARα. PPAR Research،Vol. 2014, no. 2014, pp.1-10.
https://search.emarefa.net/detail/BIM-1047266
Modern Language Association (MLA)
Vechoropoulos, Michal…[et al.]. The Proatherogenic Effect of Chronic Nitric Oxide Synthesis Inhibition in ApoE-Null Mice Is Dependent on the Presence of PPARα. PPAR Research No. 2014 (2014), pp.1-10.
https://search.emarefa.net/detail/BIM-1047266
American Medical Association (AMA)
Vechoropoulos, Michal& Ish-Shalom, Maya& Shaklai, Sigal& Sack, Jessica& Stern, Naftali& Tordjman, Karen M.. The Proatherogenic Effect of Chronic Nitric Oxide Synthesis Inhibition in ApoE-Null Mice Is Dependent on the Presence of PPARα. PPAR Research. 2014. Vol. 2014, no. 2014, pp.1-10.
https://search.emarefa.net/detail/BIM-1047266
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1047266