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Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2640-3. doi: 10.1161/ATVBAHA.112.300317. Epub 2012 Sep 20.

Apelin/APJ signaling is a critical regulator of statin effects in vascular endothelial cells--brief report.

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1
Yale University School of Medicine, Section of Cardiovascular Medicine, 300 George Street, Room 770H, New Haven, CT 06511, USA.

Abstract

OBJECTIVE:

The endothelial response elicited by the G-protein-coupled receptor pathway involving apelin and APJ predicts an overall vasoprotective effect. As a number of downstream endothelial targets of apelin/APJ signaling are also known to be targeted by statins (3-hydroxy-3-methyl-glutaryl [HMG]-CoA reductase inhibitors) as potential mediators of their known pleiotropic effects, we evaluated for the involvement of apelin/APJ signaling in statin endothelial effects.

METHODS AND RESULTS:

We found that disruption of apelin/APJ signaling in endothelial cells leads to significantly decreased expression of Krűppel-like factor 2, endothelial nitric oxide synthase, and thrombomodulin. We found that statin-mediated induction of Krűppel-like factor 2, endothelial nitric oxide synthase, and thrombomodulin expression, as well as inhibition of monocyte-endothelial adhesion, was abrogated by concurrent apelin knockdown. Moreover, we found that statins can transcriptionally regulate APJ in a Krűppel-like factor 2-dependent manner, demonstrating the presence of a positive-feedback loop.

CONCLUSIONS:

Our findings provide a novel mechanism by which the apelin/APJ pathway serves as a critical intermediary that links statin to its pleiotropic effects in regulating endothelial gene targets and function.

PMID:
22995518
PMCID:
PMC3495062
DOI:
10.1161/ATVBAHA.112.300317
[Indexed for MEDLINE]
Free PMC Article

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