CD163+ cardiac macrophages attenuate pressure overload-induced left ventricular systolic dysfunction via interleukin-10
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ABSTRACT:
PROVIDER: PRJNA1162930 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30728726_1.fastq.gz | Fastqsanger.gz | |||
| SRR30728726_2.fastq.gz | Fastqsanger.gz | |||
| SRR30728727_1.fastq.gz | Fastqsanger.gz | |||
| SRR30728727_2.fastq.gz | Fastqsanger.gz | |||
| SRR30728728_1.fastq.gz | Fastqsanger.gz |
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Project description:Background Chronic sustained pressure overload induces cardiac remodeling, which often leads to heart failure. Cardiac macrophages (cMacs) are heterogeneous cell populations, and their elimination has been shown to exacerbate pressure overload-induced heart failure. CD163, a macrophage-specific scavenger receptor expressed in a subset of cMacs, has been linked to cardiovascular events through its serum soluble form. This study aimed to elucidate the functional role of the CD163+ cMacs subset in pressure overload-induced heart failure. Methods Transverse aortic constriction (TAC) was performed on wild-type and CD163-deficient (Cd163-/-) mice to investigate the role of CD163 in pressure overload-induced cardiac remodeling and heart failure. Echocardiography was used to assess heart structure and function. Transcriptomic analysis and transmission electron microscopy were employed to observe mitochondrial structure in cardiomyocytes. Flow cytometry was used to quantify cMacs and cytokine-expressing cMacs in the heart. Additionally, serum samples from hypertensive patients with and without heart failure were analyzed to explore the relationship between CD163 and heart failure. Results TAC-induced left ventricular systolic dysfunction, including reduced ejection fraction and fractional shortening, was significantly aggravated in Cd163-/- mice post-surgery. Genes differentially expressed due to CD163 deficiency were enriched in pathways related to mitochondrial bioenergetics and homeostasis. Transmission electron microscopy revealed an increase in dysfunctional mitochondria in cardiomyocytes of Cd163-/- mice post-TAC. Additionally, decreased serum interleukin (IL)-10 levels and reduced IL-10 expression in cMacs were observed in Cd163-/- mice post-TAC. IL-10 supplementation significantly reversed TAC-induced reductions in left ventricular systolic function and improved mitochondrial bioenergetics and homeostasis in Cd163-/- mice. Conclusions The protective functions of CD163 in cMacs are associated with IL-10 expression during pressure overload-induced heart failure.
2025-05-08 | GSE277624 | GEO
Project description:Cardiac macrophages (cMacs) elimination exacerbates pressure overload-induced heart failure. However, the role of functionally distinct subsets of cMacs in heart failure remains largely unknown. CD163, a macrophage-specific scavenger receptor expressed in a subset of cMacs, has been associated with cardiovascular events through its circulating soluble form. This study aimed to elucidate the functional role of the CD163+ cMacs subset in pressure overload-induced heart failure. Transverse aortic constriction (TAC) was used to induce pressure overload. TAC-induced left ventricular systolic dysfunction, characterized by reduced ejection fraction and fractional shortening, was significantly aggravated in Cd163−/− mice post-surgery. Genes differentially expressed due to CD163 deficiency were enriched in pathways related to mitochondrial bioenergetics and homeostasis. Transmission electron microscopy revealed an increase in dysfunctional mitochondria in cardiomyocytes of Cd163−/− mice post-TAC. Additionally, decreased serum interleukin (IL)-10 levels and reduced IL-10 expression in cMacs were observed in Cd163−/− mice post-TAC. IL-10 supplementation significantly reversed TAC-induced reductions in left ventricular systolic function in Cd163−/− mice and improved mitochondrial functions in cardiomyocytes. Furthermore, decreased IL-10 levels and increased soluble CD163 were identified as risk factors for heart failure in hypertensive patients. Thus, CD163 in cMacs attenuates pressure overload-induced left ventricular systolic dysfunction through IL-10.
2025-05-08 | GSE223346 | GEO
Project description:Lionheart LincRNA Alleviates Cardiac Systolic Dysfunction under Pressure Overload
| PRJNA644194 | ENA
Project description:BACKGROUND: Cardiac hypertrophy compensates for increased biomechanical stress of the heart induced by prevalent cardiovascular pathologies, but can result in cardiac failure if left untreated. We hypothesized that the tail-anchored protein Dysferlin with multiple Ca2+-binding C2-domains is critical for the integrity of the transverse-axial tubule (TAT) network inside cardiomyocytes, and contributes to the proliferation of TAT endomembranes during pressure overload-induced cardiac hypertrophy. OBJECTIVE: To reveal the impact of the membrane fusion and repair protein Dysferlin on TAT network stabilization and proliferation necessary for the hypertrophic growth of cardiomyocytes. METHODS AND RESULTS: Super-resolution light and electron microscopy of mouse cardiomyocytes identified a specific localization of Dysferlin in a vesicular compartment in nanometric proximity to contact sites of the TAT network with the sarcoplasmic reticulum (SR), a.k.a. junctional complexes for Ca2+-induced Ca2+ release. Mass spectrometry was used to characterize the cardiac Dysferlin interactome, thereby identifying a novel protein interaction with the membrane-tethering SR protein Juncophilin-2, a known interactor of L-type Ca2+ channels and Ryanodine Receptor Ca2+ release channels in junctional complexes. While the Dysferlin knockout caused a mild progressive phenotype of dilated cardiomyopathy in the mouse heart, global proteome analysis revealed changes preceding systolic failure. Following transverse aortic constriction (TAC), Dysferlin protein expression was significantly increased in hypertrophied wild-type myocardium, while Dysferlin knockout animals presented markedly reduced left-ventricular hypertrophy. Live-cell membrane imaging demonstrated a profound reorganization of the TAT network in wild-type left-ventricular myocytes post-TAC with robust proliferation of axial tubules, which critically depended on the increased expression of Dysferlin within newly-emerging tubule components. CONCLUSIONS: Dysferlin represents a new molecular target in cardiac disease that protects the integrity of tubule-SR junctional complexes for regulated excitation-contraction coupling, and controls TAT network reorganization and tubular membrane proliferation in cardiomyocyte hypertrophy induced by pressure-overload.
2024-07-15 | PXD053051 | Pride
Project description:Each heart was assigned to one of the following three conditions: phasic systolic overload (SO), phasic diastolic overload (DO), and no loading throughout the cardiac cycle (control; CN). We created SO by isovolumic contraction (peak systolic LVP > 170 mmHg) at a constant diastolic volume with end-diastolic pressure (EDP) equals 0 mmHg. For DO, we increased LVV in diastole so that EDP reached 40 mmHg, and unloaded quickly in systole to minimize LVP generation. At the end of 3 hours, the myocardium from each heart was collected for subsequent analyses. rat heart subjected to phasic systolic overload and diastolic overload
2013-02-07 | E-GEOD-44108 | biostudies-arrayexpress
Project description:Left ventricular systolic dysfunction in female NBCe1-B/C-knockout mice
| PRJNA925818 | ENA
Project description:Cardiac macrophage CD163 protects pressure overload-induced heart failure via interleukin-10
| PRJNA925852 | ENA
Project description:To look at the affect of talins in cardiac fibroblasts (CF), we subjected Tln2-null and Tln2-null; Tln1-specific CF knockout mice to AngII stimulation for 8 weeks to induce pressure overload injury. We found that Tln2-null; Tln1-specific CF knockout mice had increaed cardiomyocyte hypertrophy and systolic blood pressure, with not change in intersitial fibrosis.
2022-04-27 | GSE189323 | GEO
Project description:We tested the hypothesis that a set of differentially expressed genes could be used to predict cardiovascular phenotype in mice after prolonged catecholamine stress. Experiment Overall Design: We observed that WT FVB and B2KO mice developed systolic dysfunction in response to continuous catecholamine infusion while WT C57 mice developed diastolic dysfunction. Using these mice as the derivation cohort, we identified a set of 83 genes whose differential expression correlated with left ventricle systolic dysfunction. The gene set was then used to accurately predict development of left ventricle systolic dysfunction in a separate group of mice (WT B6129SF2/J) after catecholamine stress.
2009-10-26 | E-GEOD-12413 | biostudies-arrayexpress
Project description:Heart failure due to chronic volume overload (VO) in rats and humans is characterized by disorganization of the cardiomyocyte desmin/mitochondrial network. Here, we tested the hypothesis that desmin breakdown is an early and continuous process throughout VO. Male Sprague-Dawley rats had aortocaval fistula (ACF) or sham surgery and were examined 24 h and 4 and 12 wk later. Desmin/mitochondrial ultrastructure was examined by transmission electron microscopy (TEM) and immunohistochemistry (IHC). Protein and kinome analysis were performed in isolated cardiomyocytes, and desmin cleavage was assessed by mass spectrometry in left ventricular (LV) tissue. Echocardiography demonstrated a 40% decrease in the LV mass-to-volume ratio with spherical remodeling at 4 wk with ACF and LV systolic dysfunction at 12 wk. Starting at 24 h and continuing to 4 and 12 wk, with ACF there is TEM evidence of extensive mitochondrial clustering, IHC evidence of disorganization associated with desmin breakdown, and desmin protein cleavage verified by Western blot analysis and mass spectrometry. IHC results revealed that ACF cardiomyocytes at 4 and 12 wk had perinuclear translocation of αB-crystallin from the Z disk with increased α, β-unsaturated aldehyde 4-hydroxynonelal. Use of protein markers with verification by TUNEL staining and kinome analysis revealed an absence of cardiomyocyte apoptosis at 4 and 12 wk of ACF. Significant increases in protein indicators of mitophagy were countered by a sixfold increase in p62/sequestosome-1, which is indicative of an inability to complete autophagy. An early and continuous disruption of the desmin/mitochondrial architecture, accompanied by oxidative stress and inhibition of apoptosis and mitophagy, suggests its causal role in LV dilatation and systolic dysfunction in VO.NEW & NOTEWORTHY This study provides new evidence of early onset (24 h) and continuous (4-12 wk) desmin misarrangement and disruption of the normal sarcomeric and mitochondrial architecture throughout the progression of volume overload heart failure, suggesting a causal link between desmin cleavage and mitochondrial disorganization and damage.
| S-EPMC5538858 | biostudies-literature