An assay for macrophage-mediated regulation of endothelial cell proliferation (original) (raw)
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Proliferating Macrophages Populate Established Atherosclerotic Lesions
Circulation Research, 2014
A new study reveals that the majority of macrophages in established atherosclerotic lesions are derived from local proliferation rather than from the influx of blood-borne monocytes. Although the factors driving proliferation remain to be understood, the findings suggest that targeting macrophage proliferation could represent a new therapeutic opportunity in established atherosclerosis.
Soluble Mediators Produced by Pro-Resolving Macrophages Inhibit Angiogenesis
Frontiers in Immunology
Different subtypes of macrophages have been shown to participate in different stages of inflammation and tissue repair. In the late stage of tissue repair, the macrophages, following their engulfment of apoptotic neutrophils, acquire a new phenotype termed alternatively activated macrophages. These macrophages produce growth factors, such as vascular endothelial growth factor (VEGF), that facilitate the angiogenic response as part of tissue restoration. Then, in the later stages of tissue healing, capillary regression takes place. It is presently unknown whether macrophages play an antiangiogenic role in the final stages of tissue repair. Here, we examined whether soluble mediators secreted by pro-resolving CD11b low macrophages (Mres) inhibit angiogenesis in the context of the resolution of tissue repair. Our findings indicate that soluble mediators produced by ex vivo generated Mres (CM-Mres) attenuate angiogenesis in vitro by inhibiting human umbilical vein endothelial cell (HUVEC) proliferation by lowering their cyclin D1 expression. In addition, CM-Mres lowered HUVEC survival by inducing caspase 3/7 activation, and also inhibited VEGFR2 activation via VEGF. HUVEC migration and differentiation to tubular-like structure was also inhibited by CM-Mres. Similarly, CM-Mres significantly inhibited neovascularization as depicted ex vivo by utilizing the rat aorta ring assay and in vivo by utilizing the chick chorioallantoic membrane assay. Notably endostatin, which was shown previously to exert its antiangiogenic effect by inhibiting proliferation, survival, motility, and morphogenesis of endothelial cells via inhibition of VEGFR2 activation, is produced by Mres. Taken together, our results suggest that a specialized subset of macrophages that appear during the resolution of inflammation can produce antiangiogenic mediators, such as endostatin. These mediators can halt angiogenesis, thereby restoring tissue structure.
Erciyes Medical Journal, 2021
Knowlege of the mechanism of atherosclerosis in chronic and inflammatory diseases is important in health care management. According to the World Health Organization, approximately 17.9 million people die from atherosclerosis annually. Macrophages played a major role in the immune response and pathophysiology of atherosclerosis. This review presents the role of macrophage in the development of atherosclerosis.
Diverse Roles of Macrophages in Atherosclerosis: From Inflammatory Biology to Biomarker Discovery
Mediators of Inflammation, 2012
Cardiovascular disease, a leading cause of mortality in developed countries, is mainly caused by atherosclerosis, a chronic inflammatory disease. Macrophages, which differentiate from monocytes that are recruited from the blood, account for the majority of leukocytes in atherosclerotic plaques. Apoptosis and the suppressed clearance of apoptotic macrophages (efferocytosis) are associated with vulnerable plaques that are prone to rupture, leading to thrombosis. Based on the central functions of macrophages in atherogenesis, cytokines, chemokines, enzymes, or microRNAs related to or produced by macrophages have become important clinical prognostic or diagnostic biomarkers. This paper discusses the impact of monocyte-derived macrophages in early atherogenesis and advanced disease. The role and possible future development of macrophage inflammatory biomarkers are also described.
Clinical significance of macrophage phenotypes in cardiovascular disease
Clinical and Translational Medicine, 2014
The emerging understanding of macrophage subsets and their functions in the atherosclerotic plaque has led to the consensus that M1 macrophages are pro-atherogenic while M2 macrophages may promote plaque stability, primarily though their tissue repair and anti-inflammatory properties. As such, modulating macrophage function to promote plaque stability is an exciting therapeutic prospect. This review will outline the involvement of the different macrophage subsets throughout atherosclerosis progression and in models of regression. It is evident that much of our understanding of macrophage function comes from in vitro or small animal models and, while such knowledge is valuable, we have much to learn about the roles of the macrophage subsets in the clinical setting in order to identify the key pathways to target to possibly promote plaque stability.
Journal of Leukocyte Biology, 1985
The mature murine macrophage-like cells NCTC-3749 and J-774, the immature human macrophage-like cells U-937-1, and their conditioned media exhibited potent angiogenic activity in rat corneas and stimulated proliferation of bovine aortic endothelial cells (BAEC) and DNA synthesis in BALB/c-3T3 cells in culture. In contrast, the immature human macrophage-like cells HL-60 and their conditioned media either failed to produce or release detectable quantities of these activities. Exposure of HL-60 cells to phorbol-myristate-acetate (PMA) did not enhance expression of angiogenic and growth stimulating activities by these cells. Both the angiogenic and growth stimulating activities appear to be mediated by a factor(s) that has biochemical properties in common with macrophage-derived growth factor (MDGF) produced by normal rat peritoneal macrophages. These results suggest that NCTC-3749, J-774, and U-937-1 macrophage-like cell lines may be a useful source for the large scale production and characterization of MDGF and macrophage-derived angiogenic activity.
Dual role of macrophages in tumor growth and angiogenesis
Journal of Leukocyte Biology, 2006
During the neoplastic progression, macrophages as well as dendritic and NK cells are attracted into the tumor site and initiate the immune response against transformed cells. They activate and present tumor antigens to T cells, which are then activated to kill tumor cells. However, tumor cells are often capable of escaping the immune machinery. As the immune surveillance is not sufficient anymore, tumor-associated macrophages contribute to tumor progression. It is notable that tumor-associated macrophages promote the proliferation of tumor cells directly by secreting growth factors. They also participate in tumor progression by acting on endothelial cells and thus promoting the neovascularization of the tumor. Tumor-associated macrophages are indeed key protagonists during angiogenesis and promote each step of the angiogenesis cascade.
Journal of Innate Immunity, 2012
The macrophage is exquisitely sensitive to its microenvironment, as demonstrated primarily through in vitro study. Changes in macrophage phenotype and function within the atherosclerotic plaque have profound consequences for plaque biology, including rupture and arterial thrombosis leading to clinical events such as myocardial infarction. We review the evidence for dynamic changes in macrophage numbers and macrophage differentiation within the atherosclerotic plaque microenvironment and discuss potential approaches to target macrophage differentiation for therapeutic benefit in cardiovascular disease.