Asprosin induces vascular endothelial-to-mesenchymal transition in diabetic lower extremity peripheral artery disease
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Published:2022-02-15
Issue:1
Volume:21
Page:
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ISSN:1475-2840
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Container-title:Cardiovascular Diabetology
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language:en
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Short-container-title:Cardiovasc Diabetol
Author:
You Mei,Liu Yushuang,Wang Bowen,Li Li,Zhang Hexuan,He Hongbo,Zhou Qing,Cao Tingbing,Wang Lijuan,Zhao Zhigang,Zhu Zhiming,Gao Peng,Yan Zhencheng
Abstract
Abstract
Background
Altered adipokine secretion in dysfunctional adipose tissue facilitates the development of atherosclerotic diseases including lower extremity peripheral artery disease (PAD). Asprosin is a recently identified adipokine and displays potent regulatory role in metabolism, but the relationship between asprosin and lower extremity PAD remains uninvestigated.
Methods
33 type 2 diabetes mellitus (T2DM) patients (DM), 51 T2DM patients with PAD (DM + PAD) and 30 healthy normal control (NC) volunteers were recruited and the blood samples were collected for detecting the circulatory asprosin level and metabolomic screening. RNA sequencing was performed using the aorta tissues from the type 2 diabetic db/db mice and human umbilical vein endothelial cells (HUVECs) were treated with asprosin to determine its impact on the endothelial-to-mesenchymal transition (EndMT).
Results
The circulating levels of asprosin in DM + PAD group were significantly higher than that of NC group and the DM group. Circulating asprosin level was remarkably negatively correlated with ankle-brachial index (ABI), even after adjusting for age, sex, body mass index (BMI) and other traditional risk factors of PAD. Logistic regression analysis revealed that asprosin is an independent risk factor for PAD and receiver-operator characteristic (ROC) curve determined a good sensitivity (74.5%) and specificity (74.6%) of asprosin to distinguish PAD. Data from metabolomics displayed a typical characteristics of de novo amino acid synthesis in collagen protein production by myofibroblasts in patients with PAD and activation of TGF-β signaling pathway appeared in the aortic tissue of db/db mice. Asprosin directly induces EndMT in HUVECs in a TGF-β-dependent manner as TGF-β signaling pathway inhibitor SB431542 erased the promotional effect of asprosin on EndMT.
Conclusions
Elevated circulatory asprosin level is an independent risk factor of lower extremity PAD and might serve as a diagnostic marker. Mechanistically, asprosin directly induces EndMT that participates in vascular injury via activation of TGF-β signaling pathway.
Trial registration This trial was registered at clinicaltrials.gov as NCT05068895
Funder
Key Technologies Research and Development Program National Natural Science Foundation of China Natural Science Foundation of Chongqing Project of Army Medical Center of PLA
Publisher
Springer Science and Business Media LLC
Subject
Cardiology and Cardiovascular Medicine,Endocrinology, Diabetes and Metabolism
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