Weight Loss Using an mHealth App Among Individuals With Obesity in Different Economic Regions of China: Cohort Study.

Background: With the increasing prevalence of obesity, weight loss has become a critical issue in China. Self-managed weight loss through a mobile health (mHealth) app may be a prospective method. However, its practicability in different economic regions of China is unknown. Objective: This study aims to evaluate the effectiveness of self-managed weight loss through an mHealth app among individuals with obesity in different economic regions of China and to demonstrate the feasibility of online self-management for weight loss. Methods: A total of 165,635 Chinese adults who signed up for the mHealth app were included to analyze the body composition characteristics of individuals from different economic regions by χ2 analyses. Furthermore, 2 types of participants with obesity using mHealth monitoring, including 74,611 participants with a BMI ≥24.0 kg/m2 and 22,903 participants with a normal BMI but an excessive percentage of body fat (PBF), were followed for 6 months to explore the weight loss and fat loss effects in different economic regions of China and to find independent predictors associated with weight loss success by 2-tailed Student t test and multivariable logistic regression analysis. Results: There were 32,129 users from low-income regions and 133,506 users from high-income regions. The proportion of users with obesity in low-income regions was higher than in high-income regions, both based on BMI (15,378/32,129, 47.9% vs 59,233/133,506, 44.4%; P<.001) and PBF classification (19,146/32,129, 59.6% vs 72,033/133,506, 54%; P<.001). Follow-up analyses showed that the weight loss effect among participants with overweight or obesity in low-income regions was greater than in high-income regions (mean -4.93, SD 6.41 vs mean -4.71, SD 6.14 kg; P<.001), while there was no significant difference in fat loss (mean -2.06%, SD 3.14% vs mean -2.04%, SD 3.19%; P=.54). In the population with normal-weight obesity, the weight loss (mean -2.42, SD 4.07 vs mean -2.23, SD 4.21 kg; P=.004) and fat loss effects (mean -1.43%, SD 2.73% vs mean -1.27%, SD 2.63%; P<.001) were stronger in high-income regions than in low-income regions. In addition, multivariable logistic regression analyses showed that age, baseline PBF, skeletal muscle rate, and measurement frequency were related to weight loss, whereas gender and baseline body metabolic rate only showed a correlation with weight loss in the population in high-income regions. Conclusions: This study found a high proportion of mHealth app users with obesity in low-income regions. Individuals with overweight and obesity in different economic regions of China experienced significant weight loss and fat loss using an mHealth app. Moreover, individuals in high-income regions paid more attention to body fat and had better fat reduction effects. Therefore, promoting self-monitoring of weight and PBF through an mHealth app could be an important intervention that could be implemented across all regions of China.

TREM2 macrophage promotes cardiac repair in myocardial infarction by reprogramming metabolism via SLC25A53.

Efferocytosis and metabolic reprogramming of macrophages play crucial roles in myocardial infarction (MI) repair. TREM2 has been proven to participate in phagocytosis and metabolism, but how it modulates myocardial infarction remains unclear. In this study, we showed that macrophage-specific TREM2 deficiency worsened cardiac function and impaired post-MI repair. Using RNA-seq, protein and molecular docking, and Targeted Metabolomics (LC-MS), our data demonstrated that macrophages expressing TREM2 exhibited decreased SLC25A53 transcription through the SYK-SMAD4 signaling pathway after efferocytosis, which impaired NAD+ transport into mitochondria, downregulated SLC25A53 thereby causing the breakpoint in the TCA cycle and subsequently increased itaconate production. In vitro experiments confirmed that itaconate secreted by TREM2+ macrophages inhibited cardiomyocyte apoptosis and promoted fibroblast proliferation. Conversely, overexpression of TREM2 in macrophages could improve cardiac function. In summary, our study reveals a novel role for macrophage-specific TREM2 in MI, connecting efferocytosis to immune metabolism during cardiac repair.

Endothelial TET2 regulates the white adipose browning and metabolism via fatty acid oxidation in obesity.

Obesity is a complex metabolic disorder, manifesting as excessive accumulation of body fat. Ten-Eleven Translocation-2 (TET2) has garnered significant attention in the context of obesity due to its crucial role in epigenetic regulation and metabolic homeostasis. In this study, we aimed to investigate the effect of endothelial TET2 on obesity and explore the potential mechanism. We generated endothelial cell-specific TET2 deficiency mice and investigated endothelial TET2 using transcriptomic and epigenomic analyses. We determined the downregulation of endothelial TET2 in white adipose tissues. Furthermore, we identified that endothelial TET2 loss aggravated high-fat diet-induced obesity by inhibiting vascularization and thus suppressing white adipose tissue browning. Mechanistically, endothelial TET2 modulates obesity by engaging in endothelial fatty acid oxidation and angiocrine-mediated secretion of bone morphogenetic protein 4 (BMP4), in which nuclear factor-erythroid 2-related factor 2 (NRF2) serves as a key mediator. Our study reveals that endothelial TET2 regulates white adipose tissue browning by interacting with NRF2 to facilitate fatty acid oxidation and lipolysis in adipocytes.

[Retrospective clinical study of hip replacement in the treatment of traumatic arthritis secondary to acetabular fracture].

OBJECTIVE: To investigate the clinical effect of total hip replacement (THA) in the treatment of traumatic arthritis secondary to acetabular fracture. METHODS: From October 2019 to June 2022, 15 patients with secondary traumatic arthritis of acetabulum fracture were treated with THA. There were 8 males and 7 females, aged from 40 to 76 years old with an average of (59.20±9.46) years old. Prosthesis loosening, dislocation of hip joint, range of motion of hip joint, nerve injury and other conditions were recorded before and after surgery. Harris score, visual analogue scale (VAS) and imaging were used to evaluate hip joint function and surgical effect. RESULTS: Follow-up time ranged 6 to 39 months with an average of (18.33±9.27) months. All the 15 patients successfully completed the operation, no nerve and blood vessel injury during the operation, postoperative wound healing was stageⅠ, no infection, one case of acetabular side prosthesis loosening at half a year after operation, and recovered well after revision surgery, one case of hip dislocation was cured after open reduction treatment, no adverse consequences. Harris score at the last postoperative follow-up was (88.60±4.01) points, compared with the preoperative (47.20±11.77) points, the difference was statistically significant (P<0.05), and VAS at the lateat postoperative follow-up was 1 (1) points, compared with the preoperative 8 (2) points, the difference was statistically significant (P<0.05). At the last follow-up, the pain symptoms were relieved or disappeared, and the joint function was satisfactory. The imaging data of the latest follow-up showed joint was well pseudoradiated, no abnormal ossification occurred, and the prosthesis was not loose. CONCLUSION: THA is effective in the treatment of traumatic arthritis secondary to acetabular fracture and can effectively improve the quality of life of patients. Preoperative comprehensive evaluation and bone defect evaluation of patients, and intraoperative management of acetabulum, femur, internal fixation and bone defect are key factors for the success of surgery.

ROR2 deficit may induce the tetralogy of Fallot via down-regulating of ß-catenin/SOX3/HSPA6 in vitro and in vivo.

Tetralogy of Fallot (TOF) is the highly conventional appearance of cyanotic congenital heart disease. Our study aimed to assess the involvement of receptor tyrosine kinase-like orphan receptor 2 (ROR2) in TOF and elucidate the specific mechanism. Upon investigation of human tissue samples, we observed a decrease in ROR2 expression in TOF patients compared to healthy control individuals. Transcriptome analysis revealed diminished ROR2 expression in TOF pathological samples relative to normal tissues. Of the 2246 genes that exhibited altered expression, 886 were upregulated, while 1360 were down-regulated. KEGG analysis and GO analysis of the differentially expressed genes indicated that these genes were significantly enriched in the Wnt signalling pathway, apoptosis and cardiac development function. Importantly, ROR2 was the only gene shared among the three pathways. Furthermore, interference with ROR2 promotes apoptosis and curtails cell proliferation in vitro. The knockdown of the ROR2 gene in AC16 cells resulted in a significant decrease in Edu-positive cells. Flow cytometry studies indicated an increase in the percentage of cells in the S phase. In contrast, the G2/M cell cycle transition was blocked in the ROR2-knockdown group, leading to a significant increase in apoptosis. Moreover, the CCK-8 cell viability assay demonstrated a reduced proliferation in the ROR2-knockdown group. Furthermore, both in vivo and in vitro data indicated that the expression of HSPA6 (Recombinant Heat Shock 70 kDa Protein6), an essential gene enriched in cardiac tissue and associated with apoptosis, was down-regulated following ROR2 knockdown mediated by the ß-catenin/SOX3 signalling pathway. In conclusion, low expression of ROR2 plays a crucial role in the occurrence and development of TOF, which may be related to the downregulation of HSPA6 through the ß-catenin/SOX3 signalling pathway.

NLRC3 deficiency promotes hypoxia-induced pulmonary hypertension development via IKK/NF-κB p65/HIF-1α pathway.

Hypoxia-induced pulmonary hypertension is a subgroup of type 3 pulmonary hypertension (PH) with the recommended treatment limited to oxygen therapy and lacks potential therapeutic targets. To investigate the role of NLRC3 in hypoxia-induced PH and its potential mechanism, we first collected lung tissues of high-altitude pulmonary hypertension (HAPH) patients. Immunohistochemistry and immunofluorescence showed that NLRC3 was downregulated and was mainly co-localized with the smooth muscle cells of the pulmonary vessels in HAPH patients. Besides, we found that NLRC3 was also expressed in endothelial cells in HAPH patients for the first time. Then, wild type (WT) and NLRC3 knockout (NLRC3-/-) mice were used to construct hypoxia models and primary pulmonary arterial smooth muscle cells (PASMCs) of rats and endothelial cells were cultured for verification. Right heart catheterization and echocardiography suggested that NLRC3 knockout promoted right ventricular systolic pressure (RVSP) up-regulation, right ventricular hypertrophy and fibrosis in hypoxia-induced mice. This study first demonstrated that NLRC3 deficiency promoted hypoxia-stimulated PASMCs proliferation, Human umbilical vein endothelial cells (HUVECs) apoptosis, migration and inflammation through IKK/NF-κB p65/HIF-1α pathway in vitro and in vivo, further promoted vascular remodeling and PH progression, which provided a new target for the treatment of hypoxia-induced PH.

Macrophage-Specific NLRC5 Protects From Cardiac Remodeling Through Interaction With HSPA8.

Macrophages regulate inflammation and the process of tissue repair. Therefore, a better understanding of macrophages in the pathogenesis of heart failure is needed. In patients with hypertrophic cardiomyopathy, NLRC5 was significantly increased in circulating monocytes and cardiac macrophages. Myeloid-specific deletion of NLRC5 aggravated pressure overload-induced pathological cardiac remodeling and inflammation. Mechanistically, NLRC5 interacted with HSPA8 and suppressed NF-κB pathway in macrophages. The absence of NLRC5 in macrophages promoted the secretion of cytokines such as interleukin-6 (IL-6), which affected cardiomyocyte hypertrophy and cardiac fibroblast activation. Tocilizumab, an anti-IL-6 receptor antagonist, may be a novel therapeutic strategy for cardiac remodeling and chronic heart failure.

Loss of TET2 impairs endothelial angiogenesis via downregulating STAT3 target genes.

BACKGROUND: Ischemic diseases represent a major global health care burden. Angiogenesis is critical in recovery of blood flow and repair of injured tissue in ischemic diseases. Ten-eleven translocation protein 2 (TET2), a member of DNA demethylases, is involved in many pathological processes. However, the role of TET2 in angiogenesis is still unrevealed. METHODS: TET2 was screened out from three DNA demethylases involved in 5-hydroxylmethylcytosine (5-hmC) regulation, including TET1, TET2 and TET3. Knockdown by small interfering RNAs and overexpression by adenovirus were used to evaluate the role of TET2 on the function of endothelial cells. The blood flow recovery and density of capillary were analyzed in the endothelial cells-specific TET2-deficient mice. RNA sequencing was used to identify the TET2-mediated mechanisms under hypoxia. Co-immunoprecipitation (Co-IP), chromatin immunoprecipitation-qPCR (ChIP-qPCR) and glucosylated hydroxymethyl-sensitive-qPCR (GluMS-qPCR) were further performed to reveal the interaction of TET2 and STAT3. RESULTS: TET2 was significantly downregulated in endothelial cells under hypoxia and led to a global decrease of 5-hmC level. TET2 knockdown aggravated the hypoxia-induced dysfunction of endothelial cells, while TET2 overexpression alleviated the hypoxia-induced dysfunction. Meanwhile, the deficiency of TET2 in endothelial cells impaired blood flow recovery and the density of capillary in the mouse model of hindlimb ischemia. Mechanistically, RNA sequencing indicated that the STAT3 signaling pathway was significantly inhibited by TET2 knockdown. Additionally, Co-IP, ChIP-qPCR and GluMS-qPCR further illustrated that STAT3 recruited and physically interacted with TET2 to activate STAT3 target genes. As expected, the effects of TET2 overexpression were completely suppressed by STAT3 silencing in vitro. CONCLUSIONS: Our study suggests that the deficiency of TET2 in endothelial cells impairs angiogenesis via suppression of the STAT3 signaling pathway. These findings give solid evidence for TET2 to be a therapeutic alternative for ischemic diseases.

Extracellular traps from activated vascular smooth muscle cells drive the progression of atherosclerosis.

Extracellular DNA traps (ETs) represent an immune response by which cells release essential materials like chromatin and granular proteins. Previous studies have demonstrated that the transdifferentiation of vascular smooth muscle cells (VSMCs) plays a crucial role in atherosclerosis. This study seeks to investigate the interaction between CD68+ VSMCs and the formation of ETs and highlight its function in atherosclerosis. Here we show that ETs are inhibited, and atherosclerotic plaque formation is alleviated in male Myh11CrePad4flox/flox mice undergoing an adeno-associated-virus-8 (AAV8) mediating overexpression of proprotein convertase subtilisin/kexin type 9 mutation (PCSK9) injection and being challenged with a high-fat diet. Obvious ETs generated from CD68+ VSMCs are inhibited by Cl-amidine and DNase I in vitro. By utilizing VSMCs-lineage tracing technology and single-cell RNA sequencing (scRNA-seq), we demonstrate that the ETs from CD68+ VSMCs influence the progress of atherosclerosis by regulating the direction of VSMCs' transdifferentiation through STING-SOCS1 or TLR4 signaling pathway.

Self-managed weight loss by smart body fat scales ameliorates obesity-related body composition during the COVID-19 pandemic: A follow-up study in Chinese population.

Background: Since 2020, longer stay-at-home time in response to the coronavirus disease 2019 (COVID-19) pandemic has changed the weight-related behaviors of Chinese population. Objectives: To explore the demographic and basic characteristics of body fat scale users and to investigate the changes in obesity-related body composition of overweight and obese users during COVID-19. Further, we analyzed the factors associated with successful weight loss and improved body composition changes in overweight and obese people. Methods: The study included 107,419 Chinese adults registered in the smart app connecting to the body fat scale in 2020 to describe the demographic characteristics of body fat scale users by Unpaired Student's t-test and Chi-Square test. Subsequently, overweight and obese participants with body mass index (BMI) of more than 24 kg/m2 were screened to investigate the independent factors associated with effective weight loss and improved body composition changes by multivariable logistic regression analyses. Results: During the pandemic, the number of body fat scale users increased markedly compared with pre-pandemic. Over half of the participants were women and with normal baseline BMI. Based on BMI classification, multivariable logistic regressions showed that age, gender, measurement frequency classification, baseline BMI, visceral adipose index and skeletal muscle rate were associated with weight loss and fat loss in the overweight and obese population, with the high-frequency measurement being the most important factor for effective weight and fat loss. In the population with normal BMI obesity, younger age was the most significant factor for effective fat loss. Conclusion: During the COVID-19 pandemic, participation in self-monitored weight loss increased markedly compared with pre-pandemic, and women accounted for the majority. We found that many overweight and obese participants achieved weight loss goals by smart body fat scales, and the effectiveness of weight and fat loss was greater in obese participants than in overweight participants, both based on BMI and PBF classification. In addition, promoting the usage of smart body fat scales could contribute to more effective weight and fat loss in the overweight and obese population based on BMI classification. However, in the population with normal BMI obesity, young subjects might be easier to successfully lose fat compared with the elder. Digital self-management by smart body fat scales could become a promising approach for the obese population with high BMI to lose weight and keep healthy.

Assessment of Effect of Perceived Social Support on School Readiness, Mental Wellbeing, and Self-Esteem: Mediating Role of Psychological Resilience.

Objective of this study is to investigate the impact of perceived social support on the self-esteem, mental wellbeing, and school readiness of left-behind (LB) children. It further aims at understanding the mediating role of psychological resilience between the relationships of perceived social support and self-esteem, mental wellbeing, and school readiness. For this purpose, population frame of the LB children between the ages of 8-12 years in Mainland China was taken. The sample size of 335 was taken to reach the findings through partial least square (PLS) structural equation modeling. The SmartPLS has been used to analyze the data. The results obtained in this study have shown that the perceived social support plays a very significant role in enhancing the mental wellbeing, self-esteem, and school readiness of the LB children. It has also been found that the perceived social support plays a positive role in the psychological resilience. Furthermore, it has also been found that the psychological resilience is an important predictor of self-esteem and school readiness. Further, the psychological resilience has proved to be significant mediator between the relationship of the perceived social support and self-esteem; and also between the relationship of the perceived social support and school readiness.

The Association and Pathogenesis of SERPINA3 in Coronary Artery Disease.

Background: Serine proteinase inhibitor A3 (SERPINA3) has been discovered in the pathogenesis of many human diseases, but little is known about the role of SERPINA3 in coronary artery disease (CAD). Therefore, we aim to determine its relationship with CAD and its function in the pathogenesis of atherosclerosis. Methods: In total 86 patients with CAD and 64 patients with non-CAD were compared. The plasma SERPINA3 levels were measured using ELISA. Logistic regression analysis and receiver-operating characteristic (ROC) analysis were performed to illustrate the association between plasma SERPINA3 levels and CAD. In vitro, real-time PCR (RT-PCR) and immunofluorescence staining were used to determine the expression of SERPINA3 in atherosclerotic plaques and their component cells. Then rat aortic smooth muscle cells (RASMCs) were transfected with siRNA to knock down the expression of SERPINA3 and human umbilical vein endothelial cells (HUVECs) were stimulated by SERPINA3 protein. EdU assay and scratch assay were used for assessing the capability of proliferation and migration. The cell signaling pathway was evaluated by western blot and RT-PCR. Results: Patients with CAD [104.4(54.5-259.2) µg/mL] had higher levels of plasma SERPINA3 than non-CAD [65.3(47.5-137.3) µg/mL] (P = 0.004). After being fully adjusted, both log-transformed and tertiles of plasma SERPINA3 levels were significantly associated with CAD. While its diagnostic value was relatively low since the area under the ROC curve was 0.64 (95% CI: 0.55-0.73). Secreted SERPINA3 might increase the expression of inflammatory factors in HUVECs. Vascular smooth muscle cells had the highest SERPINA3 expression among the aorta compared to endothelial cells and inflammatory cells. The knockdown of SERPINA3 in RASMCs attenuated its proliferation and migration. The phosphorylated IκBα and its downstream pathway were inhibited when SERPINA3 was knocked down. Conclusions: Elevated plasma SERPINA3 levels were associated with CAD. SERPINA3 can increase inflammatory factors expression in HUVECs. It can regulate VSMCs proliferation, migration, and releasing of inflammatory factors through the NF-κB signaling pathway. Thus, SERPINA3 played a significant role in the pathogenesis of atherosclerosis.

The subcellular redistribution of NLRC5 promotes angiogenesis via interacting with STAT3 in endothelial cells.

Angiogenesis is a critical step in repair of tissue injury. The pattern recognition receptors (PRRs) recognize pathogen and damage associated molecular patterns (DAMPs) during injury and achieve host defense directly. However, the role of NLR family CARD domain containing 5 (NLRC5), an important member of PPRs, beyond host defense in angiogenesis during tissue repair remains unknown. Methods:In vitro, western blot and real-time PCR (RT-PCR) were used to detect the expression of NLRC5 in endothelial cells (ECs). Immunofluorescence microscopy was used to reveal the subcellular location of NLRC5 in ECs. Cell proliferation, wound healing, tube formation assays of ECs were performed to study the role of NLRC5 in angiogenesis. By using Tie2Cre-NLRC5flox/flox mice and bone marrow transplantation studies, we defined an EC-specific role for NLRC5 in angiogenesis. Mechanistically, co-immunoprecipitation studies and RNA sequencing indicated that signal transducer and activator of transcription 3 (STAT3) was the target of NLRC5 in the nucleus. And Co-IP was used to verify the specific domain of NLRC5 binding with STAT3. ChIP assay determined the genes regulated by interaction of STAT3 and NLRC5. Results: Knockdown of NLRC5 in vitro or in vivo inhibited pathological angiogenesis, but had no effect on physiological angiogenesis. NLRC5 was also identified to bind to STAT3 in the nucleus required the integrated death-domain and nucleotide-binding domain (DD+NACHT domain) of NLRC5. And the interaction of STAT3 and NLRC5 could enhance the transcription of angiopoietin-2 (Ang2) and cyclin D1 (CCND1) to participate in angiogenesis. Conclusions: In the ischemic microenvironment, NLRC5 protein accumulates in the nucleus of ECs and enhances STAT3 transcriptional activity for angiogenesis. These findings establish NLRC5 as a novel modulator of VEGFA signaling, providing a new target for angiogenic therapy to foster tissue regeneration.

Identification of Three Significant Genes Associated with Immune Cells Infiltration in Dysfunctional Adipose Tissue-Induced Insulin-Resistance of Obese Patients via Comprehensive Bioinformatics Analysis.

BACKGROUND: Low-grade chronic inflammation in dysfunctional adipose tissue links obesity with insulin resistance through the activation of tissue-infiltrating immune cells. Numerous studies have reported on the pathogenesis of insulin-resistance. However, few studies focused on genes from genomic database. In this study, we would like to explore the correlation of genes and immune cells infiltration in adipose tissue via comprehensive bioinformatics analyses and experimental validation in mice and human adipose tissue. METHODS: Gene Expression Omnibus (GEO) datasets (GSE27951, GSE55200, and GSE26637) of insulin-resistant individuals or type 2 diabetes patients and normal controls were downloaded to get differently expressed genes (DEGs), and GO and KEGG pathway analyses were performed. Subsequently, we integrated DEGs from three datasets and constructed commonly expressed DEGs' PPI net-works across datasets. Center regulating module of DEGs and hub genes were screened through MCODE and cytoHubba in Cytoscape. Three most significant hub genes were further analyzed by GSEA analysis. Moreover, we verified the predicted hub genes by performing RT qPCR analysis in animals and human samples. Besides, the relative fraction of 22 immune cell types in adipose tissue was detected by using the deconvolution algorithm of CIBERSORT (Cell Type Identification by Estimating Relative Subsets of RNA Transcripts). Furthermore, based on the significantly changed types of immune cells, we performed correlation analysis between hub genes and immune cells. And, we performed immunohistochemistry and immunofluorescence analysis to verify that the hub genes were associated with adipose tissue macrophages (ATM). RESULTS: Thirty DEGs were commonly expressed across three datasets, most of which were upregulated. DEGs mainly participated in the process of multiple immune cells' infiltration. In protein-protein interaction network, we identified CSF1R, C1QC, and TYROBP as hub genes. GSEA analysis suggested high expression of the three hub genes was correlated with immune cells functional pathway's activation. Immune cell infiltration and correlation analysis revealed that there were significant positive correlations between TYROBP and M0 macrophages, CSF1R and M0 macrophages, Plasma cells, and CD8 T cells. Finally, hub genes were associated with ATMs infiltration by experimental verification. CONCLUSIONS: This article revealed that CSF1R, C1QC, and TYROBP were potential hub genes associated with immune cells' infiltration and the function of proinflammation, especially adipose tissue macrophages, in the progression of obesity-induced diabetes or insulin-resistance.

miR­124­3p regulates angiogenesis in peripheral arterial disease by targeting STAT3.

Peripheral arterial disease (PAD) is the third leading cause of cardiovascular morbidity worldwide, after coronary artery disease and stroke. As endogenous regulators of gene expression, microRNAs (miRs) are implicated in the development and progression of various diseases, including types of cancer, autoimmune diseases and heart diseases. In the present study, the role of miR­124­3p in PAD was investigated. The reverse transcription­quantitative PCR results indicated that the expression levels of miR­124­3p were significantly increased in the ischemic tissue of the hindlimb ischemia (HLI) model and in hypoxic human umbilical vein endothelial cells compared with the corresponding control groups. Proliferation, wound healing and tube formation assays demonstrated the inhibition of miR­124­3p on angiogenesis in vitro and the HLI model indicated the same function of miR­124­3p in vivo. A dual­luciferase reporter revealed STAT3 as the target of miR­124­3p. The expression levels of miR­124­3p in human blood were negatively correlated with ankle­brachial index, which is an index for the evaluation of the severity of PAD. Collectively, the present study indicated that miR­124­3p was a critical regulator of angiogenesis in PAD, and a potential diagnostic, prognostic and therapeutic target for PAD.