Therapeutic silencing Spp1 in cardiac macrophages suppresses atrial fibrillation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE272503 | GEO | 2024/09/12
REPOSITORIES: GEO
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Project description:Therapeutic silencing Spp1 in cardiac macrophages suppresses atrial fibrillation
| PRJNA1136982 | ENA
Project description:In atrial fibrillation, disturbed electrical conduction disrupts the coordinated contraction of the heart’s antechambers, increasing the risk of stroke and heart failure. The rising prevalence of this disease approaches 9% in patients >65 years. Studying freshly isolated human atrial tissue and a new mouse model, we here decipher how immune and stromal cells contribute to the structural tissue remodeling that underlies atrial fibrillation. Single-cell transcriptomes from control and diseased human atria documented macrophage doubling at the expense of endothelial and mural cells. An inflammatory monocyte and a pro-fibrotic SPP1+ macrophage cluster expanded in patients with atrial fibrillation. To experimentally perturb pathways observed in patients, we matched their risk factors Hypertension, Obesity and Mitral valvE Regurgitation (HOMER) in mice. Atrial single-cell transcriptomes obtained in HOMER mice, which developed enlarged, fibrillation-prone atria, recapitulated human cell composition and transcriptome variations. Recruitment drove the expansion of atrial macrophages; accordingly, inhibition of monocyte migration reduced arrhythmia in Ccr2-/- HOMER mice. Deleting Spp1 established macrophage-derived osteopontin as a pleiotropic signal that promotes atrial fibrillation through pro-fibrotic, inflammatory crosstalk with an arsenal of local immune and stromal cells. Taken together, we identify SPP1+ macrophages as targets for immunomodulatory therapy in atrial fibrillation.
2023-07-13 | GSE224947 | GEO
Project description:In atrial fibrillation, disturbed electrical conduction disrupts the coordinated contraction of the heart’s antechambers, increasing the risk of stroke and heart failure. The rising prevalence of this disease approaches 9% in patients >65 years. Studying freshly isolated human atrial tissue and a new mouse model, we here decipher how immune and stromal cells contribute to the structural tissue remodeling that underlies atrial fibrillation. Single-cell transcriptomes from control and diseased human atria documented macrophage doubling at the expense of endothelial and mural cells. An inflammatory monocyte and a pro-fibrotic SPP1+ macrophage cluster expanded in patients with atrial fibrillation. To experimentally perturb pathways observed in patients, we matched their risk factors Hypertension, Obesity and Mitral valvE Regurgitation (HOMER) in mice. Atrial single-cell transcriptomes obtained in HOMER mice, which developed enlarged, fibrillation-prone atria, recapitulated human cell composition and transcriptome variations. Recruitment drove the expansion of atrial macrophages; accordingly, inhibition of monocyte migration reduced arrhythmia in Ccr2-/- HOMER mice. Deleting Spp1 established macrophage-derived osteopontin as a pleiotropic signal that promotes atrial fibrillation through pro-fibrotic, inflammatory crosstalk with an arsenal of local immune and stromal cells. Taken together, we identify SPP1+ macrophages as targets for immunomodulatory therapy in atrial fibrillation.
2023-07-13 | GSE197518 | GEO
Project description:In atrial fibrillation, disturbed electrical conduction disrupts the coordinated contraction of the heart’s antechambers, increasing the risk of stroke and heart failure. The rising prevalence of this disease approaches 9% in patients >65 years. Studying freshly isolated human atrial tissue and a new mouse model, we here decipher how immune and stromal cells contribute to the structural tissue remodeling that underlies atrial fibrillation. Single-cell transcriptomes from control and diseased human atria documented macrophage doubling at the expense of endothelial and mural cells. An inflammatory monocyte and a pro-fibrotic SPP1+ macrophage cluster expanded in patients with atrial fibrillation. To experimentally perturb pathways observed in patients, we matched their risk factors Hypertension, Obesity and Mitral valvE Regurgitation (HOMER) in mice. Atrial single-cell transcriptomes obtained in HOMER mice, which developed enlarged, fibrillation-prone atria, recapitulated human cell composition and transcriptome variations. Recruitment drove the expansion of atrial macrophages; accordingly, inhibition of monocyte migration reduced arrhythmia in Ccr2-/- HOMER mice. Deleting Spp1 established macrophage-derived osteopontin as a pleiotropic signal that promotes atrial fibrillation through pro-fibrotic, inflammatory crosstalk with an arsenal of local immune and stromal cells. Taken together, we identify SPP1+ macrophages as targets for immunomodulatory therapy in atrial fibrillation.
2023-07-13 | GSE225671 | GEO
Project description:Atrial fibrillation (AF) is the most common heart arrhythmia disease. The greatest risk of atrial fibrillation is stroke, and stroke caused by valvular heart disease with atrial fibrillation (AF-VHD) is more serious. the development mechanism from VHD to AF-VHD is not yet clear. The research on expression profiles of lncRNA and mRNA is helpful to explore molecular mechanism in patients with valvular heart disease who develop atrial fibrillation.
2018-04-12 | GSE113013 | GEO
Project description:Atrial fibrillation (AF) is the most common persistent arrhythmia that affect 1–2% of the general population. People with AF display an array of complications cardiogenic stroke and systemic embolism caused by hemodynamic instability and blood hypercoagulability in clinical practice. However, it’s still unclear whether and how ubiquitylated proteins react to AF in the left atrial appendage of patients with AF and valvular heart disease. This theory focuses on the changes of ubiquitylated proteins in atrial fibrillation associated with heart valve disease. We firstly widely analysis the proteins ubiquitination in patients with atrial fibrillation.
2021-12-24 | PXD030397 | Pride
Project description:This study will report the incidence of atrial fibrillation after elective colorectal cancer resection in the over 65 age group. This will be used to validate a risk model for the development of post-operative atrial fibrillation.
Eligible patients will undergo electrocardiogram based screening for atrial fibrillation, as well as brain natriuretic peptide tests prior to surgery. They will undergo 24 hour holter monitor prior to surgery, and at 30 and 90 days following surgery.
The primary outcome will be occurrence of atrial fibrillation within 90 days of surgery. Secondary outcomes include quality of life change, use of hospital services for atrial fibrillation, and complications of atrial fibrillation. This will be used to validate the pre-existing model for prediction of atrial fibrillation.
| 2312263 | ecrin-mdr-crc
Project description:Atrial fibrillation (AF) is the most common sustained arrhythmia with increased risk of stroke and congestive heart failure. AF is a highly genetic heterogeneous disease, but a large proportion of AF cannot be explained by genetic variants only. Some risk factors of AF, tendentious heritable phenomenon, potentially reversible conditions and some subtypes without DNA sequence variation all indicate the participation of DNA methylation in the pathogenesis of AF. Bisulphite converted DNA from the 11 left atrium samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip GPL13534
2014-10-28 | E-GEOD-62727 | biostudies-arrayexpress
Project description:Atrial fibrillation (AF) is currently the most prevalent arrhythmia worldwide.Recent clinical data implicate the additional contribution of non-coding RNAs in the pathogenesis of AFï¼which include microRNAs(miRNAs), endogenous small interfering RNAs, PIWIinteracting RNAs, and lncRNA. Notably, a growing number of lncRNAs have been implicated in disease etiology, although an association with AF has not been reported. In the present study, we conducted an integrated analysis of dysregulated lncRNA and mRNA expression profiles in myocardial sleevesof pulmonary veins between the patients who develop AF and the patients who were in normal sinus rhythm, which was performed using a second generation lncRNA microarrayï¼focusing specifically on the identification and characterization of lncRNAs and mRNA potentially involving in maintaining atrial fibrillation. We conducted an integrated analysis of myocardial sleeves of pulmonary veinsï¼PVsï¼from 12 patients (6 non-AF and 6AF) in our center, of which hypertension, diabetes, smoking and alcohol abuse were excluded, using a second generation lncRNA microarray
2016-01-16 | E-GEOD-76899 | biostudies-arrayexpress
Project description:Atrial fibrillation (AF), a common cardiac arrhythmia, is more prevalent in patients with elevated interleukin (IL)-1β levels. Our study shows that 15-day IL-1β injections sensitize mice to AF, inducing fibrosis, β-pleated protein accumulation in the atria, and systemic inflammation resembling AF patients. Increased caspase-1 and IL-1β maturation in the left atrium and elevated Il1b and Casp1 transcription in resident macrophages—dependent on IL-1 receptor (IL-1R)—indicate a positive feedback loop. IL-1β shortened action potentials (APs), accelerating AP and Ca2+ transient restitution, and AF sensitivity required shortened APs, caspase-1, and IL-1R. Cre-Lox knockout models revealed IL-1β signaling relies on IL-1R in macrophages, not cardiomyocytes. While Ccr2-/- mice, lacking recruited macrophages, remained AF-susceptible, mice with IL-1R deletion in cardiac resident macrophages were protected. We present a novel IL-1β-driven AF etiology mediated by IL-1R in cardiac resident macrophages and caspase-1, offering insights into therapeutic targets and distinct AF etiologies.
2024-12-16 | GSE284265 | GEO