Crosstalk of platelets with macrophages and fibroblasts aggravates inflammation, aortic wall stiffening, and osteopontin release in abdominal aortic aneurysm

Cardiovascular Research, Journal Year: 2023, Volume and Issue: 120(4), P. 417 - 432

Published: Nov. 15, 2023

Abdominal aortic aneurysm (AAA) is a highly lethal disease with progressive dilatation of the abdominal aorta accompanied by degradation and remodelling vessel wall due to chronic inflammation. Platelets play an important role in cardiovascular diseases, but their AAA poorly understood.

Language: Английский

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IL-1β-induced epithelial cell and fibroblast transdifferentiation promotes neutrophil recruitment in chronic rhinosinusitis with nasal polyps

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Oct. 22, 2024

Neutrophilic inflammation contributes to multiple chronic inflammatory airway diseases, including asthma and rhinosinusitis with nasal polyps (CRSwNP), is associated an unfavorable prognosis. Here, using single-cell RNA sequencing (scRNA-seq) profile human mucosa obtained from the inferior turbinates, middle of CRSwNP patients, we identify two IL-1 signaling-induced cell subsets—LY6D+ club cells IDO1+ fibroblasts—that promote neutrophil recruitment by respectively releasing S100A8/A9 CXCL1/2/3/5/6/8 into regions. IL-1β, a pro-inflammatory cytokine involved in signaling, induces transdifferentiation LY6D+ fibroblasts primary epithelial fibroblasts, respectively. In LPS-induced neutrophilic mouse model, blocking IL-1β activity receptor antagonist significantly reduces numbers mitigates inflammation. This study implicates function subsets demonstrates IL-1-based intervention for mitigating CRSwNP. Chronic (CRS) has clinical presentations without (NP). Here authors characterize CRS NP (CRSwNP) show that disease characterized signaling via cells, similar phenotype functional can be demonstrated models.

Language: Английский

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Macrophages in vascular disease: Roles of mitochondria and metabolic mechanisms

Vascular Pharmacology, Journal Year: 2024, Volume and Issue: 156, P. 107419 - 107419

Published: Aug. 23, 2024

Macrophages are a dynamic cell type of the immune system implicated in pathophysiology vascular diseases and major contributor to pathological inflammation. Excessive macrophage accumulation, activation, polarization is observed aortic aneurysm (AA), atherosclerosis, pulmonary arterial hypertension. In general, macrophages become activated polarized pro-inflammatory phenotype, which dramatically changes behavior infiltrative. These types cumbersome fail be cleared by normal mechanisms such as autophagy. The result hyper-inflammatory environment causing recruitment adjacent cells circulating further augment inflammatory response. AA, this leads excessive ECM degradation chemokine secretion, ultimately dominate landscape wall. monocytes recruited wall, where they polarize phenotype induce pathway activation. This development foam cells, significantly contribute neointima necrotic core formation atherosclerotic plaques. Pro-inflammatory macrophages, affect other diseases, present with fragmented mitochondria corresponding metabolic dysfunction. Targeting mitochondrial dynamics has proved an exciting potential therapeutic approach combat disease. review will summarize polarization, accumulation diseases.

Language: Английский

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Development of a Novel Hierarchically Biofabricated Blood Vessel Mimic Decorated with Three Vascular Cell Populations for the Reconstruction of Small‐Diameter Arteries

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 34(7)

Published: Nov. 3, 2023

Abstract The availability of grafts to replace small‐diameter arteries remains an unmet clinical need. Here, the validated methodology is reported for a novel hybrid tissue‐engineered vascular graft that aims match natural structure small‐size arteries. blood vessel mimic (BVM) comprises internal conduit co‐electrospun gelatin and polycaprolactone (PCL) nanofibers (corresponding tunica intima artery), reinforced by additional layer PCL aligned fibers (the elastic membrane). Endothelial cells are deposited onto luminal surface using rotative bioreactor. A bioprinting system extrudes two concentric cell‐laden hydrogel layers containing respectively smooth muscle pericytes create media adventitia. semi‐automated cellularization process reduces production maturation time 6 days. After evaluation mechanical properties, cellular viability, hemocompatibility, suturability, BVM successfully implanted in left pulmonary artery swine. showed good hemostatic capability withstand pressure, patency at 5 weeks post‐implantation. These promising data open new avenue developing artery‐like product reconstructing vessels.

Language: Английский

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The oral microbiota: new insight into intracranial aneurysms

Annals of Medicine, Journal Year: 2025, Volume and Issue: 57(1)

Published: Jan. 13, 2025

Background Intracranial aneurysms (IAs) are a significant clinical concern, with detection rates increasing due to advances in imaging technologies. However, precise mechanisms underlying their pathophysiology remain incompletely understood. Recent evidence suggests pivotal role of oral microbiota dysbiosis, particularly periodontal pathogens, systemic inflammation that may contribute IA development and rupture.

Language: Английский

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Chemokine (C-C Motif) Ligand 2 Expressing Adventitial Fibroblast Expansion During Loeys-Dietz Syndrome Aortic Aneurysm Formation

Arteriosclerosis Thrombosis and Vascular Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

BACKGROUND: Loeys-Dietz syndrome (LDS), caused by mutations in the TGF-β (transforming growth factor-β) signaling cascade, leads to aggressive thoracic aneurysms. While vascular smooth muscle cell (SMC) phenotype modulation has been implicated aneurysm formation, we sought characterize role of state transitions LDS pathogenesis. METHODS: We performed single-cell transcriptomic characterization aortic root/ascending aorta from a murine model ( Tgfbr2 G357W/+ versus littermate WT [wild-type] control) at 8 weeks, 24 and samples human surgical specimens (n=5 [ TGFBR1/2 ] n=2 donor understand alterations LDS. Select markers were spatially localized with RNA situ hybridization, immunofluorescence, immunohistochemistry. Single-cell sequencing (>30 000 cells) revealed unique SMC, fibroblast, macrophage profiles RESULTS: Instead SMC phenotypic seen Marfan syndrome, observed are most prominent adventitial fibroblast mouse model. distinct modulated cluster does not appear , SMCs transcriptomically differ counterparts. Adventitial fibroblasts activated into proinflammatory associated increased recruitment Ccl2 Il6 Ccl7 Cxcl2 ) fibrotic response genes Col1a1 Col1a2 Col3a1 ), 6-fold increase wall content compared WT. Similar findings also program parallel heightened recruitment. CONCLUSIONS: Despite similarities dominant cellular molecular mechanism aneurysms distinct. modulate state. fibroblasts, addition SMCs, another important pathological population during formation consider for targeted therapy potentially impede formation.

Language: Английский

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Single-cell RNA sequencing identifies two fibroblast subtypes and a Trem2+ macrophage subtype as the possible specific cellular targets in abdominal aortic aneurysms

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: May 20, 2025

Background Aortic aneurysm is a potentially fatal condition. Although contemporary studies have established that this disease triggers an inflammatory response, reduces smooth muscle cells, and induces extracellular matrix remodeling, the involvement of cells associated signaling pathways in progression expansion aneurysms well-documented. However, clinical treatments utilizing anti-inflammatory therapies proven ineffective. Methods In study, we employed classic mouse model abdominal aortic (AAA) to compare cellular composition functional phenotypes normal AAA within comprehensive single-cell microenvironment. Results Our findings revealed distinct evolutionary for both fibroblasts macrophages, leading identification specific fibroblast subtypes (Fib_Apoc1 + /Fabp4 inflam-Fib1) macrophage subtype (Mac_TREM2). Cellular interactome analysis further reveals macrophages may play certain synergistic role development AAA. This study provides characterization transcriptional landscape identifies novel therapeutic targets.

Language: Английский

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Paradoxical Changes: EMMPRIN Tissue and Plasma Levels in Marfan Syndrome-Related Thoracic Aortic Aneurysms

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(6), P. 1548 - 1548

Published: March 8, 2024

Background: Thoracic aortic aneurysms (TAAs) associated with Marfan syndrome (MFS) are unique in that extracellular matrix metalloproteinase inducer (EMMPRIN) levels do not behave the way they other cardiovascular pathologies. EMMPRIN is shed into circulation through secretion of vesicles. This has been demonstrated to be dependent upon Membrane Type-1 MMP (MT1-MMP). We investigated this relationship MFS TAA tissue and plasma discern why profiles may exist. Methods: Protein targets were measured from patients TAAs compared healthy controls. The abundance location MT1-MMP was modified fibroblasts secreted conditioned culture media. Results: elevated but reduced plasma, Tissue elevation did induce MMP-3, MMP-8, or TIMP-1 expression, while TIMP-2 elevated. MMP-2 MMP-9 increased plasma. In fibroblasts, required internalization MT1-MMP. Conclusions: MFS, impaired likely contributes higher levels, influenced by cellular localization. Low conjunction analytes, distinguished controls, suggesting diagnostic potential.

Language: Английский

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Roles and mechanism of IL-11 in vascular diseases

Frontiers in Cardiovascular Medicine, Journal Year: 2023, Volume and Issue: 10

Published: May 26, 2023

Vascular diseases are the leading cause of morbidity and mortality worldwide. Therefore, effective treatment strategies that can reduce risk vascular urgently needed. The relationship between Interleukin-11 (IL-11) development has gained increasing attention. IL-11, a target for therapeutic research, was initially thought to participate in stimulating platelet production. Additional research concluded IL-11 is treating several diseases. However, function mechanism these remain unknown. This review summarizes expression, function, signal transduction mechanism. study also focuses on role coronary artery disease, hypertension, pulmonary cerebrovascular aortic other its potential as target. Consequently, this provides new insight into clinical diagnosis

Language: Английский

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The Endothelial Transcription Factor ERG Mediates a Differential Role in the Aneurysmatic Ascending Aorta with Bicuspid or Tricuspid Aorta Valve: A Preliminary Study

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10848 - 10848

Published: Sept. 16, 2022

The pathobiology of ascending aorta aneurysms (AAA) onset and progression is not well understood only partially characterized. AAA are also complicated in case bicuspid valve (BAV) anatomy. There emerging evidence about the crucial role endothelium-related pathways, which show an altered expression function. Here, we examined involvement ERG-related pathways differential disease aortic tissues from patients having a BAV or tricuspid (TAV) with without AAA. Our findings identified ERG as novel endothelial-specific regulator TGF-β-SMAD, Notch, NO by modulating fibrotic calcified TAV aortas. We provided that calcification correlated to different (as gene protein), appears be under control Notch signaling. latter, when increased, associated early aortas aneurysmatic, was demonstrated favor versus severe complications, i.e., dissection rupture. In aneurysmatic aortas, appeared modulate fibrosis. Therefore, proposed may represent sensitive tissue biomarker monitor target develop therapeutic strategies influence surgical procedures.

Language: Английский

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