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Cardiovascular Drugs and Therapy
Published in: Cardiovascular Drugs and Therapy 6/2021

01-12-2021 | Sitagliptin | Original Article

Dipeptidyl Peptidase-4 Inhibitor Decreases Allograft Vasculopathy Via Regulating the Functions of Endothelial Progenitor Cells in Normoglycemic Rats

Authors: Feng-Yen Lin, Chun-Min Shih, Chun-Yao Huang, Yi-Tin Tsai, Shih-Hurng Loh, Chi-Yuan Li, Cheng-Yen Lin, Yi-Wen Lin, Chien-Sung Tsai

Published in: Cardiovascular Drugs and Therapy | Issue 6/2021

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Abstract

Purpose

Chronic rejection induces the occurrence of orthotopic allograft transplantation (OAT) vasculopathy, which results in failure of the donor organ. Numerous studies have demonstrated that in addition to regulating blood sugar homeostasis, dipeptidyl peptidase-4 (DPP-4) inhibitors can also provide efficacious therapeutic and protective effects against cardiovascular diseases. However, their effects on OAT-induced vasculopathy remain unknown. Thus, the aim of this study was to investigate the direct effects of sitagliptin on OAT vasculopathy in vivo and in vitro.

Methods

The PVG/Seac rat thoracic aorta graft to ACI/NKyo rat abdominal aorta model was used to explore the effects of sitagliptin on vasculopathy. Human endothelial progenitor cells (EPCs) were used to investigate the possible underlying mechanisms.

Results

We demonstrated that sitagliptin decreases vasculopathy in OAT ACI/NKyo rats. Treatment with sitagliptin decreased BNP and HMGB1 levels, increased GLP-1 activity and stromal cell-derived factor 1α (SDF-1α) expression, elevated the number of circulating EPCs, and improved the differentiation possibility of mononuclear cells to EPCs ex vivo. However, in vitro studies showed that recombinant B-type natriuretic peptide (BNP) and high mobility group box 1 (HMGB1) impaired EPC function, whereas these phenomena were reversed by glucagon-like peptide 1 (GLP-1) receptor agonist treatment.

Conclusions

We suggest that the mechanisms underlying sitagliptin-mediated inhibition of OAT vasculopathy probably occur through a direct increase in GLP-1 activity. In addition to the GLP-1-dependent pathway, sitagliptin may regulate SDF-1α levels and EPC function to reduce OAT-induced vascular injury. This study may provide new prevention and treatment strategies for DPP-4 inhibitors in chronic rejection-induced vasculopathy.
Appendix
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Metadata
Title
Dipeptidyl Peptidase-4 Inhibitor Decreases Allograft Vasculopathy Via Regulating the Functions of Endothelial Progenitor Cells in Normoglycemic Rats
Authors
Feng-Yen Lin
Chun-Min Shih
Chun-Yao Huang
Yi-Tin Tsai
Shih-Hurng Loh
Chi-Yuan Li
Cheng-Yen Lin
Yi-Wen Lin
Chien-Sung Tsai
Publication date
01-12-2021
Publisher
Springer US
Keyword
Sitagliptin
Published in
Cardiovascular Drugs and Therapy / Issue 6/2021
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-020-07013-w

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