ArticleCardiovascular diabetology2024
Adipsin improves diabetic hindlimb ischemia through SERPINE1 dependent angiogenesis.
Article in Cardiovascular diabetology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- The Role of SERPINE1 in Coordinating Osteogenesis and Angiogenesis of hDPSCs for Bone Regeneration.International endodontic journal · 2026Article
- Myeloid-Derived Growth Factor Improves Endothelial Progenitor Cell Function and Angiogenesis in Mice With Diabetic Hindlimb Ischemia by Activating Akt/HIF-1α Signalling Pathway.Journal of cellular and molecular medicine · 2026Article
- The impact of hydrogen sulfide on gut microbiota of diabetic mice with lower limb arterial ischemia.BMC microbiology · 2026Article
- Integration of single-cell and bulk RNA sequencing data identified an aortic dissection-enriched ANGPTL4+ macrophage subpopulation.Frontiers in immunology · 2026Article
- SERBP1: A Multifunctional RNA-Binding Protein Linking Gene Expression, Cellular Metabolism, and Diseases.Cells · 2025Review
- When Heroes Fall: Reduced Expression of Heat-Resistant Obscure Proteins in Ischemic Stroke.Neuromolecular medicine · 2025Article
- "SERBP1 (Hero45) is a Novel Link with Ischemic Heart Disease Risk: Associations with Coronary Arteries Occlusion, Blood Coagulation and Lipid Profile".Cell biochemistry and biophysics · 2025Article
- GEO combined with quantitative protein trait loci identify causative proteins in hypertrophic cardiomyopathy.ESC heart failure · 2025Article
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19 authors.
Funding
Abstract
backgroundAdipsin (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.
methodsA 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.
resultsAdipsin 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, ERK, and eNOS pathways both in vivo and in vitro. RNA sequencing and co-immunoprecipitation/mass spectrometry (Co-IP/MS) analyses identified that Adipsin promoted angiogenesis by interacting with SERBP1, which disrupted the binding of SERBP1 to SERPINE1 mRNA, resulting in reduced SERPINE1 expression and the subsequent activation of the VEGFR2 signaling cascade.
conclusionsAdipsin promotes angiogenesis and facilitates blood perfusion recovery in diabetic mice with HLI by downregulating SERPINE1 through interaction with SERBP1. These findings elucidate a novel therapeutic potential for Adipsin in the management of PAD in diabetic patients, highlighting its role in enhancing angiogenesis and tissue repair.
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