Nature Reviews Cardiology, Journal Year: 2021, Volume and Issue: 18(5), P. 368 - 379
Published: Jan. 18, 2021
Language: Английский
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: March 5, 2024
Cardiac macrophage contributes to the development of cardiac fibrosis, but factors that regulate macrophages transition and activation during this process remains elusive. Here we show, by single-cell transcriptomics, lineage tracing parabiosis, from circulating monocytes preferentially commit macrophage-to-myofibroblast (MMT) under angiotensin II (Ang II)-induced hypertension, with accompanying increased expression RNA N6-methyladenosine demethylases, ALKBH5. Meanwhile, macrophage-specific knockout ALKBH5 inhibits Ang II-induced MMT, subsequently ameliorates fibrosis dysfunction. Mechanistically, immunoprecipitation sequencing identifies interlukin-11 (IL-11) mRNA as a target for ALKBH5-mediated m6A demethylation, leading IL-11 stability protein levels. By contrast, overexpression IL11 in reverses phenotype ALKBH5-deficient mice macrophage. Lastly, targeted delivery or receptor α (IL11RA1) siRNA monocytes/macrophages attenuates MMT hypertensive stress. Our results thus suggest ALKBH5/IL-11/IL11RA1/MMT axis alters dysfunction mice, thereby identify potential targets therapy patients.
Language: Английский
Citations
26
Cardiology Research and Practice, Journal Year: 2024, Volume and Issue: 2024, P. 1 - 22
Published: May 18, 2024
Cardiomyopathy encompasses a broad spectrum of diseases affecting myocardial tissue, characterized clinically by abnormalities in cardiac structure, heart failure, and/or arrhythmias. Clinically heterogeneous, major types include dilated cardiomyopathy (DCM), hypertrophic (HCM), restrictive (RM), ischemic (ICM), among which DCM is more prevalent, while ICM exhibits higher incidence and mortality rates. Myocardial injury during progression may lead to fibrosis. Failure intervene early inhibit the process fibrosis culminate failure. Cardiac fibroblasts constitute crucial cellular components determining extent quality fibrosis, with various subpopulations exerting diverse roles progression. Despite this, understanding plasticity transcriptional regulatory networks remains limited. Therefore, this study, we conducted comprehensive single-cell analysis explore differences fibroblast subpopulations, aim providing as many useful references possible for diagnosis, prognosis, treatment cardiomyopathy. Cells mitochondrial gene expression comprising >20% total expressed genes were excluded. Differential (DEGs) stemness within subjected Gene Ontology (GO) biological processes (BP) AUCell analysis. Monocle software was employed analyze pseudo-temporal trajectory Additionally, Python package SCENIC utilized assess enrichment transcription factors activity regulators Following batch effect correction, 179,927 cells clustered into 32 clusters, designated T_NK cells, endothelial myeloid fibroblasts, pericytes, SMCs, CMs, proliferating EndoCs, EPCs. Among them, 8148 further subdivided 4 namely C0 THBS4+ Fibroblasts, C1 LINC01133+ C2 FGF7+ C3 AGT + Fibroblasts. Results from GO_BP analyses suggest that Fibroblasts be associated immune response activation, protein transport, contractile function, correlating disease Transcription factor indicates FOS most significant TF also M1 module, possibly implicated hydrolysis, intracellular DNA replication, cell proliferation. Moreover, correlation between reveals pronounced heterogeneity exhibit increased sensitivity towards adverse outcomes cardiomyopathy, such impaired compared other subpopulations. The differential subgroups offer new perspectives targeting subpopulation treat EPAS1 MYC, along regulator FOS, play modulating
Language: Английский
Citations
26
Journal of Inflammation Research, Journal Year: 2024, Volume and Issue: Volume 17, P. 1255 - 1264
Published: Feb. 1, 2024
Background: The associations of two novel inflammation biomarkers, systemic response index (SIRI) and immune (SII), with mortality risk in patients chronic heart failure (CHF) are not well-characterized. Methods: This retrospective cohort study included CHF medical centers Chinese People's Liberation Army General Hospital, Beijing, China. outcomes this in-hospital long-term mortality. Associations SIRI SII were assessed using multivariable regressions receiver operating characteristic (ROC) analyses. Results: A total 6232 the present study. We documented 97 cases 1738 during an average 5.01-year follow-up. Compared lowest quartile SIRI, those highest exhibited 134% higher (adjusted odds ratio, 2.34; 95% confidence interval [CI], 1.16– 4.72) 45% hazard 1.45; CI, 1.25– 1.67). SII, 27% 1.27; 1.11– 1.46). In ROC analyses, showed better prognostic discrimination than C-reactive protein (area under curve: 69.39 vs 60.91, P = 0.01, for mortality; 61.82 58.67, 0.03, 3-year mortality), whereas similar value protein. Conclusion: significantly associated CHF. may provide Keywords: inflammation, index, failure,
Language: Английский
Citations
21
ACS Nano, Journal Year: 2024, Volume and Issue: 18(5), P. 4443 - 4455
Published: Jan. 9, 2024
The management of myocardial ischemia/reperfusion (I/R) damage in the context reperfusion treatment remains a significant hurdle field cardiovascular disorders. injured lesions exhibit distinctive features, including abnormal accumulation necrotic cells and subsequent inflammatory response, which further exacerbates impairment cardiac function. Here, we report genetically engineered hybrid nanovesicles (hNVs), contain cell-derived overexpressing high-affinity SIRPα variants (SαV-NVs), exosomes (EXOs) derived from human mesenchymal stem (MSCs), platelet-derived (PLT-NVs), to facilitate cell clearance inhibit responses. Mechanistically, presence SαV-NVs suppresses CD47-SIRPα interaction, leading promotion macrophage phagocytosis dead cells, while component EXOs aids alleviating Moreover, PLT-NVs endow hNVs with capacity evade immune surveillance selectively target infarcted area. In I/R mouse models, coadministration showed notable synergistic effect, enhancement left ventricular ejection fraction (LVEF) on day 21. These findings highlight that possess ability alleviate inflammation, minimize infarct size, improve function offering simple, safe, robust strategy boosting repair after I/R.
Language: Английский
Citations
19
Journal of the American College of Cardiology, Journal Year: 2024, Volume and Issue: 84(17), P. 1646 - 1662
Published: Aug. 30, 2024
Inflammation is thought to be an important mechanism for the development and progression of obesity-related heart failure with preserved ejection fraction (HFpEF). In STEP-HFpEF Program, once-weekly 2.4 mg semaglutide improved failure-related symptoms, physical limitations, exercise function, reduced levels C-reactive protein (CRP), a biomarker inflammation, body weight in participants HFpEF. However, neither prevalence nor clinical characteristics patients who have various magnitudes inflammation context HFpEF been well described. Furthermore, whether beneficial effects on HF efficacy endpoints Program are modified by baseline has not fully established. Finally, relationship between reduction changes CRP across defined.
Language: Английский
Citations
19
Heliyon, Journal Year: 2024, Volume and Issue: 10(12), P. e32563 - e32563
Published: June 1, 2024
Flavonoids are found in the roots, stems, leaves, and fruits of many plant taxa. They related to growth development, pigment formation, protection against environmental stress. function as antioxidants exert anti-inflammatory effects cardiovascular system by modulating classical inflammatory response pathways, such TLR4-NF-ĸB, PI3K-AKT, Nrf2/HO-1 signalling pathways. There is increasing evidence for therapeutic flavonoids on hypertension, atherosclerosis, other diseases. The potential clinical value diseases has been widely explored. For example, studies have evaluated roles regulation blood pressure via endothelium-dependent non-endothelium-dependent pathways myocardial systolic diastolic functions influencing calcium homeostasis smooth muscle-related protein expression. also hypoglycaemic, hypolipidemic, anti-platelet, autophagy, antibacterial effects. In this paper, role mechanism were reviewed order provide reference application future.
Language: Английский
Citations
18
Nature Reviews Cardiology, Journal Year: 2024, Volume and Issue: 21(7), P. 443 - 462
Published: Jan. 26, 2024
Language: Английский
Citations
16
Journal of Molecular and Cellular Cardiology, Journal Year: 2024, Volume and Issue: 189, P. 1 - 11
Published: Feb. 22, 2024
Persistent immune activation contributes significantly to left ventricular (LV) dysfunction and adverse remodeling in heart failure (HF). In contrast their well-known essential role acute myocardial infarction (MI) as first responders that clear dead cells facilitate subsequent reparative macrophage polarization, the of neutrophils pathobiology chronic ischemic HF is poorly defined. To determine importance progression cardiomyopathy, we measured production, levels, a mouse model 8 weeks after permanent coronary artery ligation large MI. mice, were more abundant both locally failing myocardium (more border zone) systemically blood, spleen, bone marrow, together with increased BM granulopoiesis. There heightened stimuli for neutrophil recruitment trafficking HF, expression chemoattract chemokines CXCL1 CXCL5, chemotactic factors circulation. NETotic activity was vitro coordinate increases circulating extracellular traps (NETs) vivo. Neutrophil depletion either antibody-based or genetic approaches abrogated LV fibrosis at intermediate late stages HF. Moreover, analogous murine plasma milieu human decompensated strongly promoted trafficking. Collectively, these results support key tissue-injurious associated cytotoxic products cardiomyopathy suggest are potential targets therapeutic immunomodulation this disease.
Language: Английский
Citations
16
Nature Reviews Cardiology, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 2, 2025
Language: Английский
Citations
2
Nature Cardiovascular Research, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 6, 2025
Language: Английский
Citations
2