IFN-I Mediates Dysfunction of Endothelial Progenitor Cells in Atherosclerosis of Systemic Lupus Erythematosus

Ding, Xuewei; Xiang, Wei; He, Xiaoqing

doi:10.3389/fimmu.2020.581385

Cited by 28 publications

(24 citation statements)

References 191 publications

(226 reference statements)

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“…Simultaneously, the disorder of fat factor levels in patients with SLE may also increase CVD risk ( 47 ). Complement activation and endothelial injury are common in SLE patients as one of the possible mechanisms of CVD development ( 48 ). Differences in drug use might be another confounding factor.…”

Section: Discussionmentioning

confidence: 99%

Systemic Lupus Erythematosus and Cardiovascular Disease: A Mendelian Randomization Study

Gao

Kong

et al. 2022

Front. Immunol.

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BackgroundPrevious studies have shown that patients with systemic lupus erythematosus (SLE) tend to have a higher risk of cardiovascular disease (CVD), but the potential causal relationship between genetic susceptibility to SLE and CVD risk is not clear. This study systematically investigated the potential association between genetically determined SLE and the risk of CVD.MethodsThe genetic tools were obtained from genome-wide association studies of SLE and CVD, with no overlap between their participating populations. Mendelian randomization (MR) analysis was performed using inverse variance weighting as the primary method. Simultaneously, a series of repeated analyses, sensitivity analyses, and instrumental variable strength evaluations were performed to verify the reliability of our results.ResultsMR analysis showed that genetic susceptibility to SLE was associated with a higher risk of heart failure (OR=1.025, 95% CI [1.009-1.041], P=0.002), ischemic stroke (OR=1.020, 95% CI [1.005-1.034], P=0.009), and venous thromboembolism (OR=1.001, 95% CI [1.000-1.002], P=0.014). However, genetic susceptibility to SLE was negatively correlated with the risk of type 2 diabetes (OR=0.968, 95% CI [0.947-0.990], P=0.004). Sensitivity analysis found no evidence of horizontal pleiotropy or heterogeneity.ConclusionOur MR study explored the causal role of SLE in the etiology of CVD, which would help improve our understanding of the basic disease mechanisms of SLE and provide comprehensive CVD assessment and treatment for SLE patients.

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Section: Discussionmentioning

confidence: 99%

Systemic Lupus Erythematosus and Cardiovascular Disease: A Mendelian Randomization Study

Gao

Kong

et al. 2022

Front. Immunol.

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“…AS is a chronic cardiovascular disease and also one of the most frequent causes of death in the elderly [ 2 ]. Endothelial dysfunction is the starting point of AS and EPCs are closely associated with vascular endothelial function [ 25 ]. This study found that EPCs secreted EVs to deliver miR-199a-3p to inhibit SP1, thereby inhibiting EC ferroptosis and delaying vascular endothelial injury, and ultimately alleviating AS (Fig.…”

Section: Discussionmentioning

confidence: 99%

Effect of endothelial progenitor cell-derived extracellular vesicles on endothelial cell ferroptosis and atherosclerotic vascular endothelial injury

et al. 2021

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Atherosclerosis (AS) is a chronic inflammatory disorder characterized by endothelial dysfunction. Endothelial progenitor cells (EPCs) can overcome endothelial dysfunction and reduce AS risk. This study focused on the role of EPC-secreted extracellular vesicles (EPC-EVs) in AS. First, mouse EPCs and mouse aortic endothelial cells (MAECs) were isolated and identified. EVs were isolated from EPCs and identified. EPC-EVs were co-cultured with MAECs and the internalization of EVs was observed. Glutathione (GSH) consumption, reactive oxygen species (ROS) production, lipid peroxidation, and iron accumulation and cell death in endothelial cells were detected. The binding relationship between miR-199a-3p and specificity protein 1 (SP1) was confirmed using dual-luciferase and RIP assays. The mouse model of AS was established. The relationships between miR-199a-3p expression and aortic area plaque and serum pro-inflammatory factor were analyzed. The degree of atherosclerotic lesion was detected using oil red O staining and the serum inflammatory factors were detected using ELISA. Our results elicited that EPC-EVs inhibited cell death, GSH consumption, ROS production, lipid peroxidation, and iron accumulation in endothelial cells, thereby suppressing ferroptosis of endothelial cells. EPC-EVs transferred miR-199a-3p into endothelial cells. miR-199a-3p targeted SP1. Silencing miR-199a-3p or overexpression of SP1 in endothelial cells reversed the effect of EPC-EVs on ferroptosis of endothelial cells. In vivo experiments confirmed that EPC-EVs inhibited ferroptosis of endothelial cells and then alleviated the occurrence of AS via the miR-199a-3p/SP1 axis. To conclude, EPC-EVs transferred miR-199a-3p to inhibit SP1, thus repressing ferroptosis of endothelial cells and retarding the occurrence of AS.

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“…Data suggested that endothelial dysfunction is already present in SLE patients before CVD development [ 25 , 59 , 60 , 61 , 62 ]. Patients with SLE have functionally and quantitatively decreased levels of endothelial progenitor cells (EPCs) [ 25 , 63 ]. EPCs are a subpopulation of circulating stem cells involved in the repair of blood vessels [ 34 ].…”

Section: Non-traditional Pro-atherosclerotic Biomarkers In Sslementioning

confidence: 99%

Non-Traditional Pro-Inflammatory and Pro-Atherosclerotic Risk Factors Related to Systemic Lupus Erythematosus

Richter

Cardoneanu

Rezuş

et al. 2022

IJMS

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Cardiovascular diseases (CVD) are one of the leading causes of high mortality in patients with systemic lupus erythematosus (SLE). The Framingham risk score and other traditional risk factors do not fully reflect the CVD risk in SLE patients. Therefore, in order to stratify these high-risk patients, additional biomarkers for subclinical CVD are needed. The mechanisms of atherogenesis in SLE are still being investigated. During the past decades, many reports recognized that inflammation plays a crucial role in the development of atherosclerosis. The aim of this report is to present novel proinflammatory and pro-atherosclerotic risk factors that are closely related to SLE inflammation and which determine an increased risk for the occurrence of early cardiovascular events.

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IFN-I Mediates Dysfunction of Endothelial Progenitor Cells in Atherosclerosis of Systemic Lupus Erythematosus

Cited by 28 publications

References 191 publications

Systemic Lupus Erythematosus and Cardiovascular Disease: A Mendelian Randomization Study

Systemic Lupus Erythematosus and Cardiovascular Disease: A Mendelian Randomization Study

Effect of endothelial progenitor cell-derived extracellular vesicles on endothelial cell ferroptosis and atherosclerotic vascular endothelial injury

Non-Traditional Pro-Inflammatory and Pro-Atherosclerotic Risk Factors Related to Systemic Lupus Erythematosus

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