scholarly journals Roles of Bone-Marrow-Derived Cells and Inflammatory Cytokines in Neointimal Hyperplasia after Vascular Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Makoto Shoji ◽  
Shinji Koba ◽  
Youichi Kobayashi
Keyword(s):  
Bone Marrow ◽  
Inflammatory Cytokines ◽  
Vascular Injury ◽  
Neointimal Hyperplasia ◽  
Coronary Intervention ◽  
Peripheral Circulation ◽  
Percutaneous Coronary ◽  
Vascular Progenitor Cells ◽  
Bone Marrow Derived Cells ◽  
Necrosis Factor

Bone-marrow-derived cells can generate vascular progenitor cells that contribute to pathological remodeling in models of restenosis after percutaneous coronary intervention (PCI). We created models of vascular injury in mice with bone marrow transplants (BMT) to determine relationships between bone-marrow-derived cells and subsequent biological factors. Mesenchymal stromal cells (MSCs) seemed to inhibit the inflammatory reaction and help stabilize injured vascular regions through mobilizing more endogenous bone-marrow-derived (EBMD) cells to the peripheral circulation. Granulocyte-colony stimulating factor (G-CSF) mobilized more EBMD cells to the peripheral circulation, and they accumulated on the injured side of the vascular lumen. The inflammatory cytokines, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 mobilized EBMD cells that play an important role in the process of neointimal hyperplasia after vascular injury. These factors might comprise a mechanism that alters the transdifferentiation or paracrine capabilities of EBMD cells and are potential targets of treatment for patients with cardiovascular diseases.

Abstract 5551: Double Deficiency of Tumor Necrosis Factor-α and Interferon-γ in Bone Marrow-Derived Cells Prevents Neointimal Formation in a Murine Model of Vascular Injury

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Hideki Murayama ◽  
Masafumi Takahashi ◽  
Yuji Shiba ◽  
Masaya Takamoto ◽  
Hirohiko Ise ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Vascular Injury ◽  
Tumor Necrosis ◽  
Interferon Γ ◽  
Neointimal Formation ◽  
Tnf Α ◽  
Bone Marrow Derived Cells ◽  
Ifn Γ ◽  
Factor Α ◽  
Necrosis Factor

Neointimal formation after percutaneous coronary intervention (PCI), termed restenosis, limits therapeutic revascularization. Recent evidence indicates that inflammatory responses induced by inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), are involved in the progression of neointimal formation. However, the role of TNF-α and IFN-γ in the restenosis after PCI has not been fully understood. The purpose of this study is to examine the impact of TNF-α and IFN-γ in bone marrow-derived cells in the development of neointimal formation after vascular injury in mice. Wild-type (WT), TNF-α-deficient (TNF-α −/− ), IFN-γ-deficient (IFN-γ −/− ), and TNF-α/IFN-γ double-deficient (DKO) mice were subjected to wire-mediated vascular injury of the right femoral artery. Immunohistochemical analysis showed the expression of TNF-α and IFN-γ was detected in the neointimal lesion of WT mice, but these cytokines were not detected in the lesion of the corresponding deficient mice. Neointimal formation was significantly reduced after the injury in the DKO mice, compared to that in the WT, TNF-α −/− , and IFN-γ −/− mice (I/M ratio, WT: 2.28±0.17, TNF-α −/− : 2.13±0.20, IFN-γ −/− : 2.37±0.16, DKO: 1.32±0.10, p<0.05, each n=14–17). No significant difference in reendothelialization (CD31 staining) was observed among these groups. Further, vascular smooth muscle cell (α-SMA) and macrophage (F4/80) contents in the neointimal area also did not differ among the groups. The number of proliferating cell nuclear antigen (PCNA) and Ki-67 positive cells in the neointimal lesion was significantly decreased in DKO mice. To determine the contribution of bone marrow cells, we developed 3 types of bone marrow chimeric (BMT Wild→Wild , BMT DKO→Wild , and BMT Wild→DKO ) mice. The neointimal formation in BMT DKO→Wild mice was significantly reduced as compared to that in BMT Wild→Wild (I/M ratio, p<0.05, each n=7) and BMT Wild→DKO mice (p<0.05). These results suggest that the lack of TNF-α and IFN-γ in bone marrow-derived cells synergistically prevents neointimal formation after vascular injury and provide new insights into the mechanisms underlying the restenosis after PCI.

scholarly journals Pro-Inflammatory Cytokines in the Formation of the Pre-Metastatic Niche

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3752
Author(s):  
Ru Li ◽  
Annie Wen ◽  
Jun Lin
Keyword(s):  
Bone Marrow ◽  
Tumor Cells ◽  
Inflammatory Cytokines ◽  
Primary Tumor ◽  
Metastatic Progression ◽  
Colony Stimulating Factor ◽  
Metastatic Niche ◽  
Bone Marrow Derived Cells ◽  
Stimulating Factor ◽  
Pro Inflammatory Cytokines

In the presence of a primary tumor, the pre-metastatic niche is established in secondary organs as a favorable microenvironment for subsequent tumor metastases. This process is orchestrated by bone marrow-derived cells, primary tumor-derived factors, and extracellular matrix. In this review, we summarize the role of pro-inflammatory cytokines including interleukin (IL)-6, IL-1β, CC-chemokine ligand 2 (CCL2), granulocyte-colony stimulating factor (G-CSF), granulocyte–macrophage colony-stimulating factor (GM-CSF), stromal cell-derived factor (SDF)-1, macrophage migration inhibitory factor (MIF), and Chemokine (C–X–C motif) ligand 1 (CXCL1) in the formation of the pre-metastatic niche according to the most recent studies. Pro-inflammatory cytokines released from tumor cells or stromal cells act in both autocrine and paracrine manners to induce phenotype changes in tumor cells, recruit bone marrow-derived cells, and form an inflammatory milieu, all of which prime a secondary organ’s microenvironment for metastatic cell colonization. Considering the active involvement of pro-inflammatory cytokines in niche formation, clinical strategies targeting them offer ways to inhibit the establishment of the pre-metastatic niche and therefore attenuate metastatic progression. We review clinical trials targeting different inflammatory cytokines in patients with metastatic cancers. Due to the pleiotropy and redundancy of pro-inflammatory cytokines, combined therapies should be designed in the future.

scholarly journals Activation of heme oxygenase-1 by Ginkgo biloba extract differentially modulates endothelial and smooth muscle-like progenitor cells for vascular repair

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tao-Cheng Wu ◽  
Jia-Shiong Chen ◽  
Chao-Hung Wang ◽  
Po-Hsun Huang ◽  
Feng-Yen Lin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Smooth Muscle ◽  
Progenitor Cells ◽  
Heme Oxygenase ◽  
Neointimal Hyperplasia ◽  
Vascular Repair ◽  
Vascular Progenitor Cells

AbstractVascular progenitors such as endothelial progenitor cells (EPCs) and smooth muscle-like progenitor cells (SMPCs) may play different roles in vascular repair. Ginkgo biloba extract (GBE) is an exogenous activator of heme oxygenase (HO)-1, which has been suggested to improve vascular repair; however, the detailed mechanisms have yet to be elucidated. This study aimed to investigate whether GBE can modulate different vascular progenitor cells by activating HO-1 for vascular repair. A bone marrow transplantation mouse model was used to evaluate the in vivo effects of GBE treatment on wire-injury induced neointimal hyperplasia, which is representative of impaired vascular repair. On day 14 of GBE treatment, the mice were subjected to wire injury of the femoral artery to identify vascular reendothelialization. Compared to the mice without treatment, neointimal hyperplasia was reduced in the mice that received GBE treatment for 28 days in a dose-dependent manner. Furthermore, GBE treatment increased bone marrow-derived EPCs, accelerated endothelial recovery, and reduced the number of SMPCs attached to vascular injury sites. The effects of GBE treatment on neointimal hyperplasia could be abolished by co-treatment with zinc protoporphyrin IX, an HO-1 inhibitor, suggesting the in vivo role of HO-1. In this in vitro study, treatment with GBE activated human early and late EPCs and suppressed SMPC migration. These effects were abolished by HO-1 siRNA and an HO-1 inhibitor. Furthermore, GBE induced the expression of HO-1 by activating PI3K/Akt/eNOS signaling in human late EPCs and via p38 pathways in SMPCs, suggesting that GBE can induce HO-1 in vitro through different molecular mechanisms in different vascular progenitor cells. Accordingly, GBE could activate early and late EPCs, suppress the migration of SMPCs, and improve in vivo vascular repair after mechanical injury by activating HO-1, suggesting the potential role of pharmacological HO-1 activators, such as GBE, for vascular protection in atherosclerotic diseases.

scholarly journals Early vascular healing of ultra-thin strut polymer-free sirolimus-eluting stents in acute coronary syndrome: USUI-ACS study

2021 ◽  
Author(s):  
Yutaka Matsuhiro ◽  
Yasuyuki Egami ◽  
Naotaka Okamoto ◽  
Masaya Kusuda ◽  
Takashige Sakio ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Acute Coronary Syndrome ◽  
Neointimal Hyperplasia ◽  
Coronary Intervention ◽  
Median Percentage ◽  
Coronary Syndrome ◽  
Percutaneous Coronary ◽  
The Mean ◽  
Sirolimus Eluting Stent

Abstract Purpose:Ultra-thin strut polymer-free sirolimus eluting stent (UPF-SES) have two novel characteristics, ultra-thin strut and polymer-free coating, which have the potential to achieve early re-endotherialization. However, a little is known whether early vascular healing of UPF-SES can be achieved in patients with acute coronary syndrome (ACS).The aim of this study was to evaluate the vascular healing after an implantation of UPF-SES in patients with ACS using optical coherence tomography (OCT) at 3 months after the stent implantation. Methods:From September 2020 and January 2021, a total of 31 consecutive patients presenting with ACS who underwent OCT examinations at the initial percutaneous coronary intervention (PCI) and 3-month follow-up were enrolled in the USUI-ACS study. The endpoints of this study were neointimal strut coverage, malapposition, and mean neointimal hyperplasia (NIH) thickness at 3-month follow-up.Results:Over a mean follow-up of 91 days after the initial PCI, the follow-up OCT was examined. The median percentage of covered struts was 98.4% and malapposed struts 0%, and the mean NIH thickness was 60μm.Conclusions:UPF-SES exhibited an excellent early vascular healing at 3-months in patients with ACS.

scholarly journals Nanoparticles from Equine Fetal Bone Marrow-Derived Cells Enhance the Survival of Injured Chondrocytes

Animals ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1723
Author(s):  
Ki Hoon Kim ◽  
Tae Sub Park ◽  
Byung-Wook Cho ◽  
Tae Min Kim
Keyword(s):  
Bone Marrow ◽  
Inflammatory Cytokines ◽  
Interleukin 1 ◽  
Response To Treatment ◽  
Joint Diseases ◽  
Necrosis Factor Alpha ◽  
Fetal Bone ◽  
Tnf Α ◽  
Bone Marrow Derived Cells ◽  
Degenerative Joint Diseases

Recent studies have shown that mesenchymal stem cells (MSCs) can play a restorative role against degenerative joint diseases in horses. The purpose of this study was to investigate whether fetal bone marrow-derived cells (BMC)-derived nanoparticles (BMC-NPs) can stimulate the survival of equine chondrocytes. Equine fetal BMCs were isolated and characterized, and the role of BMC-NPs s in equine chondrocytes undergoing inflammatory cell death was examined. BMCs have several characteristics, such as the potential to differentiate into chondrocytes and osteocytes. Additionally, BMCs expressed immunoregulatory genes in response to treatment with tumor necrosis factor-alpha (TNF-α) and Interleukin 1 beta (IL-1β). We found that BMC-NPs were taken up by equine chondrocytes. Functionally, BMC-NPs promoted the growth of chondrocytes, and reduced apoptosis induced by inflammatory cytokines. Furthermore, we observed that BMC-NPs upregulated the phosphorylation of protein kinase B (Akt) in the presence of IL-1β, and reduced the phosphorylation of TNF-α-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the chondrocytes. Cumulatively, our study demonstrated that equine fetal BMC-NPs have the potential to stimulate the survival of chondrocytes damaged by inflammatory cytokines. Thus, BMC-NPs may become an alternative cell-free allogenic therapeutic for degenerative joint diseases in horses.

C-Reactive Protein and Inflammatory Cytokines during Percutaneous Coronary Intervention

2016 ◽  
Vol 53 (1-2) ◽  
pp. 39-48 ◽  
Author(s):  
Mingxin Wu ◽  
Xinyuan Gu ◽  
Xiujuan Li ◽  
Yanhui Li ◽  
Huaineng Zhou ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Inflammatory Cytokines ◽  
Coronary Intervention ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Percutaneous Coronary
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