AI Article Synopsis
- FoxO proteins, particularly FoxO4, are important transcription factors involved in various cellular processes related to immune function and inflammation, which are linked to atherosclerosis development.
- In experiments with apoE-deficient mice lacking FoxO4, researchers observed increased atherosclerosis and more immune cells in the plaques after a high-fat diet, indicating that FoxO4 plays a protective role.
- The findings suggest that FoxO4 may help prevent atherosclerosis by regulating inflammatory responses and oxidative stress in bone marrow-derived cells, highlighting its potential as a target for therapeutic strategies.
Article Abstract
Objectives: FoxO proteins are transcription factors involved in varieties of cellular processes, including immune cell homeostasis, cytokine production, anti-oxidative stress, and cell proliferation and differentiation. Although these processes are implicated in the development of atherosclerosis, very little is known about the role of FoxO proteins in the context of atherosclerosis. Our objectives were to determine whether and how inactivation of Foxo4, a member of the FoxO family, in vivo promotes atherosclerosis.
Methods And Results: Apolipoprotein E-deficient (apoE(-/-)) mice were crossbred with animals lacking Foxo4 (Foxo4(-/-)). After 10 weeks on a high fat diet (HFD), Foxo4(-/-)apoE(-/-) mice showed elevated atherosclerosis and increased amount of macrophages and T cells in the plaque compared to apoE(-/-) mice. Bone marrow transplantations of chimeric C57B/6 mice reconstituted with either wild-type or Foxo4(-/-) bone marrows indicate that Foxo4-deficiency in bone marrow derived cells sufficiently promoted atherosclerosis. Foxo4-null macrophages produced elevated inflammatory cytokine IL-6 and levels of reactive oxygen species (ROS) in response to lipopolysaccharides in vitro. Serum levels of IL-6 were upregulated in HFD-fed Foxo4(-/-)apoE(-/-) mice compared to those of apoE(-/-) mice.
Conclusions: FoxO4 inhibits atherosclerosis through bone marrow derived cells, possibly by inhibition of ROS and inflammatory cytokines that promote monocyte recruitment and/or retention.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226872 | PMC |
| http://dx.doi.org/10.1016/j.atherosclerosis.2011.09.038 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
How I diagnose and treat systemic mastocytosis with an associated hematologic neoplasm.
Blood
January 2025
Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom.
Over the last decade significant advances have been made by honing in on the diagnostic evaluation and the significance of molecular profiles in patients with systemic mastocytosis (SM), non-advanced and advanced.This is reflected in the 2022 iterations of the World Health Organization Edition 5 and International Consensus Criteria classifications.The impact of targeted KIT inhibitor therapies on patients treated within global trials has demonstrated significant improvements in the prognosis and overall survival for patients, leading to a change the treatment paradigm.
View Article and Find Full Text PDFHow I Treat Anemia in Myelofibrosis.
Blood
January 2025
Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, United States.
Anemia is a common consequence of myelofibrosis. The treatment of myelofibrosis-associated anemia is complicated by a multifactorial pathobiology, as well as a lack of therapies that result in normalization of the bone marrow and complete restoration of its function. Established agents that are used to treat anemia in other bone marrow failure states such as myelodysplastic syndromes and aplastic anemia, are used for the treatment of myelofibrosis-associated anemia.
View Article and Find Full Text PDFAn Activin Receptor-Like Kinase 1-governed monocytic lineage shapes an immunosuppressive landscape in breast cancer metastases.
J Clin Invest
January 2025
Department of Laboratory Medicine, Division of Translational Cancer Researc, Lund University Cancer Centre, Lund University, Lund, Sweden.
The biology centered around the TGF-beta type I receptor Activin Receptor-Like Kinase (ALK)1 (encoded by ACVRL1) has been almost exclusively based on its reported endothelial expression pattern since its first functional characterization more than two decades ago. Here, in efforts to better define the therapeutic context in which to use ALK1 inhibitors, we uncover a population of tumor-associated macrophages (TAMs) that, by virtue of their unanticipated Acvrl1 expression, are effector targets for adjuvant anti-angiogenic immunotherapy in mouse models of metastatic breast cancer. The combinatorial benefit depended on ALK1-mediated modulation of the differentiation potential of bone marrow-derived granulocyte-macrophage progenitors, the release of CD14+ monocytes into circulation, and their eventual extravasation.
View Article and Find Full Text PDFThe effects of bone marrow humoral components of B-cell acute lymphoblastic leukemia patients on natural killer cell suppression.
Immunol Res
January 2025
Department of Immunology, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Türkiye.
B-cell acute lymphoblastic leukemia (B-ALL) is the most common form of cancer diagnosed in children. While the majority of patients survive with conventional treatment, chemotherapeutic agents have adverse effects and the potential for relapse persists even after full recovery. Given their pivotal function in anti-cancer immunity, there has been a surge in research exploring the potential of natural killer (NK) cells in immunotherapy, which has emerged as a promising avenue for treating leukemia.
View Article and Find Full Text PDFEfficacy of bortezomib combined with Hyper-CVAD in adults with relapsed acute lymphoblastic leukemia or positive measurable residual disease; effect of bortezomib in leukemia.
Blood Res
January 2025
Hematology Laboratory, General Hospital of Mexico "Dr. Eduardo Liceaga", Mexico City, Mexico.
Purpose: Despite advances in the treatment of adult acute lymphoblastic leukemia (ALL), relapse remains the most significant challenge in improving prognosis. Measurable residual disease (MRD) assessment can predict bone marrow relapse based on MRD positivity. As access to innovative therapies remains limited because of the high cost, chemotherapy is the widely utilized treatment option.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!