Adipsin improves diabetic hindlimb ischemia through SERPINE1 dependent angiogenesis.

Autor: Zhang X; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Jiang M; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Zhang X; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Zuo Y; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Zhang H; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Zhang T; Xijing 986 Hospital Department, Air Force Medical University, Xi'an, China., Yang L; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Lin J; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Zhang Y; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Dai X; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Ge W; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Sun C; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Yang F; Basic Medical Teaching Experiment Center, Basic Medical College, Air Force Medical University, Xi'an, China., Zhang J; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Liu Y; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Wang Y; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Qiang H; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Yang X; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China., Sun D; Department of Cardiology, Xijing Hospital, Air Force Medical University, Xi'an, China. wintersun3@fmmu.edu.cn.
Jazyk: angličtina
Zdroj: Cardiovascular diabetology [Cardiovasc Diabetol] 2024 Dec 02; Vol. 23 (1), pp. 429. Date of Electronic Publication: 2024 Dec 02.
DOI: 10.1186/s12933-024-02526-2
Abstrakt: 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, 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.
Conclusions: Adipsin 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.
Competing Interests: Declarations. Ethics approval and consent to participate: All experimental animal procedures were approved by the Animal Care and Use Committee of the Air Force Medical University and followed the Animal Research Advisory Committee of the National Institutes of Health guidelines (Approval ID: 20201017). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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