Chronic Psychological Stress Accelerates Vascular Senescence and Impairs Ischemia‐Induced Neovascularization: The Role of Dipeptidyl Peptidase‐4/Glucagon‐Like Peptide‐1‐Adiponectin Axis

Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

卷:6

Guang Yang¹  Guangxian Zhao¹  Yanna Lei¹  Noriyuki Ouchi¹  Wenhu Xu¹  Masafumi Kuzuya¹  Enbo Zhu²  Aiko Inoue²  Lina Hu³  Xian Wu Cheng³  Kenji Okumura⁴  Rei Shibata⁴  Hongxian Wu⁴  Limei Piao⁴  Chenglin Yu⁴  Toyoaki Murohara⁴ 

[1] Geriatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan;

[2] Cardiology and ICU, Yanbian University Hospital, Yanji, Jilin Province, China;

[3] Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan;

[4] Department of Community Healthcare &

关键词: aging;    stress;    vascular biology;    vascular disease;    vascular endothelium;   

DOI  :  10.1161/JAHA.117.006421

来源: DOAJ

【 摘 要 】

BackgroundExposure to psychosocial stress is a risk factor for cardiovascular disease, including vascular aging and regeneration. Given that dipeptidyl peptidase‐4 (DPP4) regulates several intracellular signaling pathways associated with the glucagon‐like peptide‐1 (GLP‐1) metabolism, we investigated the role of DPP4/GLP‐1 axis in vascular senescence and ischemia‐induced neovascularization in mice under chronic stress, with a special focus on adiponectin ‐mediated peroxisome proliferator activated receptor‐γ/its co‐activator 1α (PGC‐1α) activation. Methods and ResultsSeven‐week‐old mice subjected to restraint stress for 4 weeks underwent ischemic surgery and were kept under immobilization stress conditions. Mice that underwent ischemic surgery alone served as controls. We demonstrated that stress impaired the recovery of the ischemic/normal blood‐flow ratio throughout the follow‐up period and capillary formation. On postoperative day 4, stressed mice showed the following: increased levels of plasma and ischemic muscle DPP4 and decreased levels of GLP‐1 and adiponectin in plasma and phospho‐AMP‐activated protein kinase α (p‐AMPKα), vascular endothelial growth factor, peroxisome proliferator activated receptor‐γ, PGC‐1α, and Sirt1 proteins and insulin receptor 1 and glucose transporter 4 genes in the ischemic tissues, vessels, and/or adipose tissues and numbers of circulating endothelial CD31+/c‐Kit+ progenitor cells. Chronic stress accelerated aortic senescence and impaired aortic endothelial sprouting. DPP4 inhibition and GLP‐1 receptor activation improved these changes; these benefits were abrogated by adiponectin blocking and genetic depletion. ConclusionsThese results indicate that the DPP4/GLP‐1‐adiponectin axis is a novel therapeutic target for the treatment of vascular aging and cardiovascular disease under chronic stress conditions.

【 授权许可】

Unknown