Histidine Triad Nucleotide-Binding Protein 1 Improves Critical Limb Ischemia by Regulating Mitochondrial Homeostasis

Critical limb ischemia (CLI) is a common complication of diabetes mellitus that typically occurs in the later stages of the disease. Vascularization is indeed an important physiological process involving the formation of new blood vessels from existing ones. It occurs in response to various normal a...

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Bibliographic Details
Published in:Nutrients 2023-11, Vol.15 (23), p.4859
Main Authors: Gao, Tingwen, Cheng, Shuo, Lu, Hao, Li, Xiao, Weng, Xinyu, Ge, Junbo
Format: Article
Language:English
Subjects:
Cardiology
Cell culture
Cell cycle
critical limb ischemia
Dextrose
Diabetes
endothelial cells
Endothelium
Flow cytometry
Glucose
Health aspects
Heart enlargement
Histidine
histidine triad nucleotide-binding protein 1
Hyperglycemia
Ischemia
Laboratory animals
Metabolism
mitochondrial dysfunction
Neovascularization
Protein binding
Proteins
Reactive oxygen species
Reagents
Veins & arteries
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Summary:Critical limb ischemia (CLI) is a common complication of diabetes mellitus that typically occurs in the later stages of the disease. Vascularization is indeed an important physiological process involving the formation of new blood vessels from existing ones. It occurs in response to various normal and pathophysiological conditions, and one of its critical roles is to compensate for inadequate oxygen supply, which is often seen in situations like chronic limb ischemia (CLI). Histidine triad nucleotide-binding protein 1 (Hint1) is a member of the Hint family that has been shown to attenuate cardiac hypertrophy, but its role in vascularization still needs to be clarified. In this study, we investigated the role of Hint1 in CLI. We found that Hint1 is significantly reduced in the muscle tissue of STZ-induced diabetic mice and high-glucose (HG)-treated endothelial cells (ECs). Hint1 deletion impaired blood flow recovery and vascularization, whereas Hint1 overexpression promoted these processes. In addition, our in vitro study showed that Hint1 deficiency aggravated mitochondrial dysfunction in ECs, as evidenced by impaired mitochondrial respiration, decreased mitochondrial membrane potential, and increased reactive oxygen species. Our findings suggest that Hint1 deficiency impairs blood perfusion by damaging mitochondrial function and that Hint1 may represent a potential therapeutic target for treating CLI.
ISSN:2072-6643
2072-6643
DOI:10.3390/nu15234859