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- Lampugnani, Maria Grazia, et al.
(författare)
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Endothelial cell disease : emerging knowledge from cerebral cavernous malformations
- 2017
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Ingår i: Current opinion in hematology. - : LIPPINCOTT WILLIAMS & WILKINS. - 1065-6251 .- 1531-7048. ; 24:3, s. 256-264
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Forskningsöversikt (refereegranskat)abstract
- Purpose of review Endothelial cells dysfunctions are crucial determinants of several human diseases. We review here the most recent reports on endothelial cell defects in cerebral cavernous malformations (CCMs), particularly focusing on adherens junctions. CCM is a vascular disease that affects specifically the venous microvessels of the central nervous system and which is caused by loss-of-function mutation in any one of the three CCM genes (CCM1, 2 or 3) in endothelial cells. The phenotypic result of these mutations are focal vascular malformations that are permeable and fragile causing neurological symptoms and occasionally haemorrhagic stroke. Recent findings CCM is still an incurable disease, as no pharmacological treatment is available, besides surgery. The definition of the molecular alterations ensuing loss of function mutation of CCM genes is contributing to orientate the testing of targeted pharmacological tools Several signalling pathways are altered in the three genotypes in a similar way and concur in the acquisition of mesenchymal markers in endothelial cells. However, also genotype-specific defects are reported, in particular for the CCM1 and CCM3 mutation. Summary Besides the specific CCM disease, the characterization of endothelial alterations in CCM has the potentiality to shed light on basic molecular regulations as the acquisition and maintenance of organ and vascular site specificity of endothelial cells.
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- Lavina, Barbara, et al.
(författare)
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New imaging methods and tools to study vascular biology
- 2015
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Ingår i: Current opinion in hematology. - 1065-6251 .- 1531-7048. ; 22:3, s. 258-266
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Forskningsöversikt (refereegranskat)abstract
- Purpose of review Throughout history, development of novel microscopy techniques has been of fundamental importance to advance the vascular biology field. This review offers a concise summary of the most recently developed imaging techniques and discusses how they can be applied to vascular biology. In addition, we reflect upon the most important fluorescent reporters for vascular research that are currently available. Recent findings Recent advances in light sheet-based imaging techniques now offer the ability to live image the vascular system in whole organs or even in whole animals during development and in pathological conditions with a satisfactory spatial and temporal resolution. Conversely, super resolution microscopy now allows studying cellular processes at a near-molecular resolution. Summary Major recent improvements in a number of imaging techniques now allow study of vascular biology in ways that could not be considered previously. Researchers now have well-developed tools to specifically examine the dynamic nature of vascular development during angiogenic sprouting, remodeling and regression as well as the vascular responses in disease situations in vivo. In addition, open questions in endothelial and lymphatic cell biology that require subcellular resolution such as actin dynamics, junctional complex formation and stability, vascular permeability and receptor trafficking can now be approached with high resolution.
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- Seignez, Cedric, et al.
(författare)
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The multitasking neutrophils and their involvement in angiogenesis
- 2017
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Ingår i: Current opinion in hematology. - 1065-6251 .- 1531-7048. ; 24:1, s. 3-8
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Forskningsöversikt (refereegranskat)abstract
- Purpose of reviewThis review describes the mechanisms by which neutrophils contribute to angiogenesis in hypoxic tissues during different conditions and diseases (e.g., menstrual cycle, wound healing, ischemic diseases, cancers), with particular focus on the recently described proangiogenic neutrophil subpopulation.Recent findingsThe importance of neutrophils in initiation of angiogenesis has been described during the past decade, and is believed to occur through release of the well-known proangiogenic factors Bv8, vascular endothelial growth factor A, and matrix metalloproteinase 9. However, additional proangiogenic actions of neutrophils have been outlined this year, mediated through for example pyruvate kinase M2, 14,15-epoxyeicosatrienoic acid, and formation of neutrophil extracellular traps, although their distinct mechanisms of action remain partly unknown. Neutrophils can also limit angiogenesis by secreting for example neutrophil elastase and -defensins, which generate angiostatic molecules and proteolytically inactivate proangiogenic factors, respectively. These opposing neutrophil actions can be the consequence of on-site education or recruitment of distinct subpopulations from circulation. Indeed, a circulating proangiogenic neutrophil subpopulation was recently described in mice and men, which was rapidly recruited to hypoxic tissues by vascular endothelial growth factor A.SummaryThese recent findings have highlighted the diversity of actions performed by neutrophils in the angiogenic process and identified new opportunities to regulate angiogenesis.
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