Journal Article

Asprosin induces vascular endothelial-to-mesenchymal transition in diabetic lower extremity peripheral artery disease

You, Mei, Zhou, Qing, Li, Li, Yan, Zhencheng, Cao, Tingbing, Liu, Yushuang, Gao, Peng, Wang, Bowen, Zhu, Zhiming, Wang, Lijuan, He, Hongbo, Zhao, Zhigang, Zhang, Hexuan

2022

Overview

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

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Adipose tissue / Amino acids / Angiology / Animals / Ankle / Aorta / Arteriosclerosis / Asprosin / Blood pressure / Body fat / Body mass index / Calcification / Cardiology / Cholesterol / Collagen / Diabetes / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - complications / Diabetes Mellitus, Type 2 - diagnosis / Endocrinology / Endothelial cells / Endothelial-to-mesenchymal transition / Endothelium, Vascular / Fibroblasts / Glucose / Human Umbilical Vein Endothelial Cells / Humans / Hypertension / Laboratories / Lower Extremity / Lower extremity peripheral artery disease / Medical imaging / Medicine / Medicine & Public Health / Mesenchyme / Metabolic syndrome / Metabolites / Metabolomics / Mice / Original Investigation / Peripheral Arterial Disease - diagnosis / Plasma / Protein biosynthesis / Risk factors / Signal transduction / TGF-β signaling pathway / Transforming growth factor-b / Type 2 diabetes mellitus / Umbilical vein / Vascular diseases / Vein & artery diseases