Mechanistic insight into premature atherosclerosis and cardiovascular complications in systemic lupus erythematosus

Liu, Yudong; Yang, Xue; Zhang, Wenduo; Zhang, Xuan; Wang, Min; Ji, Fusui

doi:10.1016/j.jaut.2022.102863

Cited by 19 publications

(14 citation statements)

References 202 publications

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“…41 Furthermore, excessive IFN levels cause activation of neutrophils and formation of extracellular traps, promoting immunologic dysregulation. 42 The present study, however, showed no correlation between IFN gene expression and clinical outcomes. As such, the effects of interferon-related transcriptions change on neutrophil functions and their relevance for pathophysiology of PAH remains to be determined.…”

Section: Discussioncontrasting

confidence: 83%

Single-Cell Transcriptome Analysis of Peripheral Neutrophils From Patients With Idiopathic Pulmonary Arterial Hypertension

Wang

Zhang²,

Zhang

et al. 2023

Hypertension

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BACKGROUND: Idiopathic pulmonary hypertension (IPAH) is a rare and devastating disease often accompanied by persistent inflammation and immune responses. We aim to provide a reference atlas of neutrophils to facilitate a better understanding of cellular phenotypes and discovery of candidate genes. METHODS: Peripheral neutrophils from naive patients with IPAH and matched controls were profiled. Whole-exon sequencing was performed to exclude known genetic mutations before establishing single-cell RNA sequencing. Marker genes were validated by flow cytometry and histology in a separate validation cohort. RESULTS: Seurat clustering analysis revealed that the landscape of neutrophils encompassed 5 clusters, including 1 progenitor, 1 transition, and 3 functional clusters. The intercorrelated genes in patients with IPAH were mainly enriched in antigen processing presentation and natural killer cell mediated cytotoxicity. We identified and validated differentially upregulated genes, including matrix metallopeptidase 9 ( MMP9 ), ISG15 ubiquitin-like modifier ( ISG15 ), and C-X-C motif ligand 8 ( CXCL8 ). The positive proportions and fluorescence quantification of these genes were significantly increased in CD16 + neutrophils in patients with IPAH. The higher proportion of positive MMP9 (matrix metallopeptidase 9) neutrophils increased mortality risk after adjustment for age and sex. Patients with higher proportions of positive MMP9 neutrophils had worse survival, while the fraction of ISG15- or C-X-C motif chemokine ligand 8-positive expression neutrophils failed to predict outcome. CONCLUSIONS: Our study yields a comprehensive dataset of the landscape of neutrophils in patients with IPAH. The predictive values of a neutrophil cluster characterized by higher MMP9 expression indicate a functional role for neutrophil-specific matrix metalloproteinases in the pathogenesis of pulmonary arterial hypertension.

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Section: Discussioncontrasting

confidence: 83%

Single-Cell Transcriptome Analysis of Peripheral Neutrophils From Patients With Idiopathic Pulmonary Arterial Hypertension

Wang

Zhang²,

Zhang

et al. 2023

Hypertension

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“…Patients treated with glucocorticoids can induce or exacerbate hyperlipidemia, disrupt vascular endothelial function, and lead to luminal narrowing [ 29 , 30 ]. These factors contribute to the development of atherosclerosis in SLE patients, leading to changes in both cardiac structure and function, and ultimately resulting in left ventricular remodeling.…”

Section: The Role Of Hcq In Slementioning

confidence: 99%

Advancements on the impact of hydroxychloroquine in systemic lupus erythematosus

Peng-Cheng,

Meng-Na,

Jian-Bin

et al. 2024

Heliyon

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“…High level of type I IFN are associated with endothelial dysfunction (ED) and endothelial cell damage in SLE (46). Vascular injury is promoted by an imbalance between endothelial damage and repair, which represents an early step in the progression of atherosclerosis (47).…”

Section: Vasculopathy In Slementioning

confidence: 99%

Ultrasound Assessment and Vascular Mechanics in Takayasu Arteritis and Systemic Lupus Erythematosus

Svensson

2023

Linköping University Medical Dissertations

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Biologic Disease-modifying antirheumatic drugs BHI Breath-holding index BMI Body mass index BP Blood pressure C3 Complement protein 3 C4 Complement protein 4 CABG Coronary artery bypass graft surgery CAD Coronary artery disease CCA Common carotid artery cDBP Central diastolic blood pressure CEUS Contrast-enhanced ultrasound CFA Common femoral artery CHD Coronary heart disease CO 2 Carbon dioxide cPP Central pulse pressure CRP C-reactive protein PapersThe papers associated with this thesis have been removed for copyright reasons. For more details about these see:

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Mechanistic insight into premature atherosclerosis and cardiovascular complications in systemic lupus erythematosus

Cited by 19 publications

References 202 publications

Single-Cell Transcriptome Analysis of Peripheral Neutrophils From Patients With Idiopathic Pulmonary Arterial Hypertension

Single-Cell Transcriptome Analysis of Peripheral Neutrophils From Patients With Idiopathic Pulmonary Arterial Hypertension

Advancements on the impact of hydroxychloroquine in systemic lupus erythematosus

Ultrasound Assessment and Vascular Mechanics in Takayasu Arteritis and Systemic Lupus Erythematosus

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