Blood vessels, disease pathogenesis, and novel therapies

and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA, .
Journal of Molecular Medicine (Impact Factor: 5.11). 03/2013; 91(3):283. DOI: 10.1007/s00109-013-1009-1
Source: PubMed
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    ABSTRACT: The first reports of circulating cells that displayed the capacity to repair and regenerate damaged vascular endothelial cells as progenitor cells for the endothelial lineage (EPC) were met with great enthusiasm. However, the cell surface antigens and colony assays used to identify the putative EPC were soon found to overlap with those of the hematopoietic lineage. Over the past decade, it has become clear that specific hematopoietic subsets play important roles in vascular repair and regeneration. This review will provide some overview of the hematopoietic hierarchy and methods to segregate distinct subsets that may provide clarity in identifying the proangiogenic hematopoietic cells. This review will not discuss those circulating viable endothelial cells that play a role as EPC and are called endothelia colony-forming cells. The review will conclude with identification of some roadblocks to progress in the field of identification of circulating cells that participate in vascular repair and regeneration.
    Journal of Molecular Medicine 01/2013; 91(3). DOI:10.1007/s00109-013-1002-8 · 5.11 Impact Factor
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    ABSTRACT: Retinal and choroidal vascular diseases constitute the most common causes of moderate and severe vision loss in developed countries. They can be divided into retinal vascular diseases, in which there is leakage and/or neovascularization (NV) from retinal vessels, and subretinal NV, in which new vessels grow into the normally avascular outer retina and subretinal space. The first category of diseases includes diabetic retinopathy, retinal vein occlusions, and retinopathy of prematurity, and the second category includes neovascular age-related macular degeneration (AMD), ocular histoplasmosis, pathologic myopia, and other related diseases. Retinal hypoxia is a key feature of the first category of diseases resulting in elevated levels of hypoxia-inducible factor-1 (HIF-1) which stimulates expression of vascular endothelial growth factor (VEGF), platelet-derived growth factor-B (PDGF-B), placental growth factor, stromal-derived growth factor-1 and their receptors, as well as other hypoxia-regulated gene products such as angiopoietin-2. Although hypoxia has not been demonstrated as part of the second category of diseases, HIF-1 is elevated and thus the same group of hypoxia-regulated gene products plays a role. Clinical trials have shown that VEGF antagonists provide major benefits for patients with subretinal NV due to AMD and even greater benefits are seen by combining antagonists of VEGF and PDGF-B. It is likely that addition of antagonists of other agents listed above will be tested in the future. Other appealing strategies are to directly target HIF-1 or to use gene transfer to express endogenous or engineered anti-angiogenic proteins. While substantial progress has been made, the future looks even brighter for patients with retinal and choroidal vascular diseases.
    Journal of Molecular Medicine 01/2008; 91(3). DOI:10.1007/s00109-013-0993-5 · 5.11 Impact Factor
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    ABSTRACT: Recent evidence suggests that processes of inflammation and angiogenesis are interconnected, especially in human pathologies. Newly formed blood vessels enable the continuous recruitment of inflammatory cells, which release a variety of proangiogenic cytokines, chemokines, and growth factors and further promote angiogenesis. These series of positive feedback loops ultimately create a vicious cycle that exacerbates inflammation, transforming it into the chronic process. Recently, this concept of reciprocity of angiogenesis and inflammation has been expanded to include oxidative stress as a novel mechanistic connection between inflammation-driven oxidation and neovascularization. Production of reactive oxygen species results from activation of immune cells by proinflammatory stimuli. As oxidative stress can lead to chronic inflammation by activating a variety of transcription factors including NF-κB, AP-1, and PPAR-γ, inflammation itself has a reciprocal relationship with oxidative stress. This review discusses the recent findings in the area bridging neovascularization and oxidation and highlights novel mechanisms of inflammation- and oxidative stress-driven angiogenesis.
    Journal of Molecular Medicine 03/2013; 91(3):323-8. DOI:10.1007/s00109-013-1007-3 · 5.11 Impact Factor


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