Abstract 12080: A Novel Adipokine Adipolin Prevents Pathological Vascular Remodeling Following Arterial Injury
Introduction: Obesity is causally linked with the development of pathological remodeling of vascular wall. Previously we have demonstrated that adipolin, also known as C1q/TNF-related protein 12, is an adipokine that is down-regulated in obese rodents. Here, we investigated whether adipolin affects vascular response to injury using loss-of-function genetic manipulations.
Methods and Results: No significant differences were observed in body weight, organ weights, blood pressure and blood glucose levels between adipolin-knockout (APL-KO) and wild type (WT) mice under basal conditions. APL-KO and WT mice were subjected to wire-induced injury of the left femoral artery. APL-KO mice exhibited an enhanced neointimal thickening after artery injury compared with WT mice. APL-KO mice also displayed an impaired re-endothelialization following vascular injury compared with WT mice. Treatment of human umbilical vein endothelial cells with recombinant adipolin protein promoted proliferation and reduced serum starvation-induced apoptosis. Adipolin treatment stimulated the phosphorylation of Akt and eNOS in endothelial cells. Pharmacological inhibition of PI3 kinase by treatment with LY294002 reversed the stimulatory effects of adipolin on endothelial cell growth and eNOS phosphorylation. Furthermore, APL-KO mice showed increased expression of pro-inflammatory cytokines including interleukin 6 and interleukin 1β in the injured artery as compared with WT mice. Consistently, treatment of mouse peritoneal macrophages with adipolin protein suppressed lipopolysaccharide-stimulated expression of pro-inflammatory mediators.
Conclusions: Our data indicate that adipolin prevents pathological remodeling of vascular walls following injury by modulating endothelial cell function and macrophage inflammatory response.
Author Disclosures: H. Ogawa: None. K. Ohashi: None. R. Shibata: None. M. Ito: None. N. Otaka: None. H. Kawanishi: None. T. Murohara: None. N. Ouchi: Research Grant; Modest; Astellas Pharma Inc., Daiichi Sankyo Co.. Honoraria; Modest; Kowa Pharmaceutical Co. Ltd..
- © 2016 by American Heart Association, Inc.