Adipsin improves diabetic hindlimb ischemia through SERPINE1 dependent angiogenesis

作者：Xiaohua Zhang, Mengyuan Jiang, Xuebin Zhang, Yixuan Zuo, Huanle Zhang, Tingting Zhang, Liyu Yang, Jie Lin, Yan Zhang, Xinchun Dai, Ge Wen, Chuang Sun, Fang Yang, Jiye Zhang, Yue Liu, Yangyang Wang, Hai Qiang, Xiaojie Yang, Dongdong Sun · 发表于：Cardiovascular Diabetology · 年份：2024 · DOI：10.1186/s12933-024-02526-2 · 被引用次数：7 · 研究领域：Adipokines, Inflammation, and Metabolic Diseases、Cardiovascular Disease and Adiposity、Adipose Tissue and Metabolism

BACKGROUND: Adipsin (complement factor D, CFD), as the first described adipokine, is well-known for its regulatory effects in diabetic cardiovascular complications. However, its role in diabetic hind-limb ischemia was not clarified. This study aimed to evaluate the possible therapeutic effect of Adipsin in hind-limb ischemia in type 2 diabetic mice and to elucidate the molecular mechanisms involved. METHODS: A high-fat diet and streptozotocin (HFD/STZ)-induced diabetic mouse model, and a transgenic mouse model with adipose tissue-specific overexpression of Adipsin (Adipsin-Tg) were employed. Hindlimb ischemia was established by femoral artery ligation, and blood flow recovery was monitored using Laser Doppler perfusion imaging. Molecular mechanisms underlying Adipsin-potentiated angiogenesis were examined using RNA sequencing and co-immunoprecipitation/mass spectrometry (Co-IP/MS) analyses. RESULTS: Adipsin expression was upregulated in non-diabetic mice following HLI, while suppressed in diabetic mice, indicating its potential role in ischemic recovery which is impaired in diabetes. Adipsin-Tg mice exhibited significantly improved blood flow recovery, increased capillary density, and enhanced muscle regeneration in comparison with non-transgenic (NTg) diabetic mice. Adipsin facilitated proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) under hyperglycemic and hypoxic conditions. Additionally, it enhanced phosphorylation of AKT, ER...