C1q/TNF-related proteins, a family of novel adipokines, induce vascular relaxation through the adiponectin receptor-1/AMPK/eNOS/nitric oxide signaling pathway.

Authors

• Qijun Zheng
• Yuexing Yuan
• Wei Yi
• Wayne Bond Lau
• Yajing Wang
• Xiaoliang Wang
• Yang Sun
• Bernard L Lopez
• Theodore A Christopher
• Jonathan M Peterson
• G William Wong
• Shiqiang Yu
• Dinghua Yi
• Xin-Liang Ma

Publication/Presentation Date

11-1-2011

Abstract

OBJECTIVE: Reduced plasma adiponectin (APN) in diabetic patients is associated with endothelial dysfunction. However, APN knockout animals manifest modest systemic dysfunction unless metabolically challenged. The protein family CTRPs (C1q/TNF-related proteins) has recently been identified as APN paralogs and some CTRP members share APN's metabolic regulatory function. However, the vasoactive properties of CTRPs remain completely unknown.

METHODS AND RESULTS: The vasoactivity of currently identified murine CTRP members was assessed in aortic vascular rings and underlying molecular mechanisms was elucidated in human umbilical vein endothelial cells. Of 8 CTRPs, CTRPs 3, 5, and 9 caused significant vasorelaxation. The vasoactive potency of CTRP9 exceeded that of APN (3-fold) and is endothelium-dependent and nitric oxide (NO)-mediated. Mechanistically, CTRP9 increased AMPK/Akt/eNOS phosphorylation and increased NO production. AMPK knockdown completely blocked CTRP9-induced Akt/eNOS phosphorylation and NO production. Akt knockdown had no significant effect on CTRP9-induced AMPK phosphorylation, but blocked eNOS phosphorylation and NO production. Adiponectin receptor 1, but not receptor 2, knockdown blocked CTRP9-induced AMPK/Akt/eNOS phosphorylation and NO production. Finally, preincubating vascular rings with an AMPK-inhibitor abolished CTRP9-induced vasorelaxative effects.

CONCLUSION: We have provided the first evidence that CTRP9 is a novel vasorelaxative adipocytokine that may exert vasculoprotective effects via the adiponectin receptor 1/AMPK/eNOS dependent/NO mediated signaling pathway.

Volume

31

Issue

11

First Page

2616

Last Page

2623

ISSN

1524-4636

Published In/Presented At

Zheng, Q., Yuan, Y., Yi, W., Lau, W. B., Wang, Y., Wang, X., Sun, Y., Lopez, B. L., Christopher, T. A., Peterson, J. M., Wong, G. W., Yu, S., Yi, D., & Ma, X. L. (2011). C1q/TNF-related proteins, a family of novel adipokines, induce vascular relaxation through the adiponectin receptor-1/AMPK/eNOS/nitric oxide signaling pathway. Arteriosclerosis, thrombosis, and vascular biology, 31(11), 2616–2623. https://doi.org/10.1161/ATVBAHA.111.231050

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

21836066

Department(s)

Administration and Leadership

Document Type

Article