Inhibition of CTRP9, a novel and cardiac-abundantly expressed cell survival molecule, by TNFα-initiated oxidative signaling contributes to exacerbated cardiac injury in diabetic mice.
Publication/Presentation Date
1-1-2013
Abstract
Recently identified as adiponectin (APN) paralogs, C1q/TNF-related proteins (CTRPs) share similar metabolic regulatory functions as APN. The current study determined cardiac expression of CTRPs, their potential cardioprotective function, and investigated whether and how diabetes may regulate cardiac CTRP expression. Several CTRPs are expressed in the heart at levels significantly greater than APN. Most notably, cardiac expression of CTRP9, the closest paralog of APN, exceeds APN by >100-fold. Cardiac CTRP9 expression was significantly reduced in high-fat diet-induced diabetic mice. In H9c2 cells, tumor necrosis factor-alpha (TNF-α) strongly inhibited CTRP9 expression (>60%), and significantly reduced peroxisome proliferator activated receptor-gamma (PPARγ), a known transcription factor promoting adiponectin expression. The inhibitory effect of TNF-α on PPARγ and CTRP9 was reversed by Tiron or rosiglitazone. CTRP9 knockdown significantly enhanced, whereas CTRP9 overexpression significantly attenuated simulated ischemia/reperfusion injury in H9c2 cells. In vivo CTRP9 administration to diabetic mice significantly attenuated NADPH oxidase expression and superoxide generation, reduced infarct size, and improved cardiac function. To the best of our knowledge, this is the first study providing evidence that downregulation of CTRP9, an abundantly expressed and novel cell survival molecule in the heart, by TNF-α-initiated oxidative PPARγ suppression contributes to exacerbated diabetic cardiac injury. Preservation of CTRP9 expression or augmentation of CTRP9-initiated signaling mechanisms may be the potential avenues for ameliorating ischemic diabetic cardiac injury.
Volume
108
Issue
1
First Page
315
Last Page
315
ISSN
1435-1803
Published In/Presented At
Su, H., Yuan, Y., Wang, X. M., Lau, W. B., Wang, Y., Wang, X., Gao, E., Koch, W. J., & Ma, X. L. (2013). Inhibition of CTRP9, a novel and cardiac-abundantly expressed cell survival molecule, by TNFα-initiated oxidative signaling contributes to exacerbated cardiac injury in diabetic mice. Basic research in cardiology, 108(1), 315. https://doi.org/10.1007/s00395-012-0315-z
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
23212557
Department(s)
Administration and Leadership
Document Type
Article