Coagulation, Fibrinolysis and Angiogenesis: New Insights from Knockout Mice

Brodsky, Sergey V.

doi:10.1159/000065305

Cited by 17 publications

(8 citation statements)

References 39 publications

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“…The importance of coagulation factors for angiogenesis is evident from the embryonic lethal vascular phenotype for many of these factors (reviewed in [191, 256]). In the adult, coagulation is also linked to angiogenesis, in particular in cancer [257–259].…”

Section: Coagulation Factorsmentioning

confidence: 99%

Manipulating angiogenesis in medicine

Carmeliet

2004

Journal of Internal Medicine

181

118

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Abstract. Carmeliet P (Center for Transgene Technology and Gene Therapy, Flanders Interuniversitary Institute for Biotechnology, KULeuven, Campus Gasthuisberg, Herestraat, Leuven, Belgium). Manipulating angiogenesis in medicine (Review). J Intern Med 2004; 255: 538-561.Blood vessels nourish organs with vital nutrients and oxygen and, thus, new vessels form when the embryo needs to grow or wounds are to heal. However, forming new blood vessels is a complex and delicate process, which, unfortunately, is often derailed. Thus, when insufficient vessels form, the tissue becomes ischaemic and stops to function adequately. Conversely, when vessels grow excessively, malignant and inflamed tissues grow faster. It is now becoming increasingly evident that abnormal vessel growth contributes to the pathogenesis of numerous malignant, ischaemic, inflammatory, infectious and immune disorders. With an in-depth molecular understanding, we should be better armamented to combat such angiogenic disorders in the future. That such therapeutic strategies might change the face of medicine is witnessed by initial evidence of success in the clinic.

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Section: Coagulation Factorsmentioning

confidence: 99%

Manipulating angiogenesis in medicine

Carmeliet

2004

Journal of Internal Medicine

181

118

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“…Recent observations have further demonstrated that MPs released from apoptotic lymphocytes or from plasma of diabetic patients induce endothelial dysfunction by modulating nitric oxide (NO) pathways (46). Angiogenesis is involved in physiological events such as embryonic development and wound healing, as well as in pathological conditions such as tumor growth, diabetic retinopathy, and chronic inflammation (8,18). This tightly regulated and complex process involves endothelial cell survival, proliferation, migration, differentiation, and tube formation (17).…”

mentioning

confidence: 99%

Lymphocytic microparticles inhibit angiogenesis by stimulating oxidative stress and negatively regulating VEGF-induced pathways

Yang

Mwaikambo²,

Zhu³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Recent studies have demonstrated that lymphocyte-derived microparticles (LMPs) impair endothelial cell function. However, no data currently exist regarding the contribution of LMPs in the regulation of angiogenesis. In the present study, we investigated the effects of LMPs on angiogenesis in vivo and in vitro and demonstrated that LMPs strongly suppressed aortic ring microvessel sprouting and in vivo corneal neovascularization. In vitro, LMPs considerably diminished human umbilical vein endothelial cell survival and proliferation in a concentration-dependent manner. Mechanistically, the antioxidants U-74389G and U-83836E were partially protective against the antiproliferative effects of LMPs, whereas the NADPH oxidase (NOX) inhibitors apocynin and diphenyleneiodonium significantly abrogated these effects. Moreover, LMPs increased not only the expression of the NOX subunits gp91(phox), p22(phox), and p47(phox), but also the production of ROS and NOX-derived superoxide (O(2)(-)). Importantly, LMPs caused a pronounced augmentation in the protein expression of the CD36 antiangiogenic receptor while significantly downregulating the protein levels of VEGF receptor type 2 and its downstream signaling mediator, phosphorylated ERK1/2. In summary, LMPs potently suppress neovascularization in vivo and in vitro by augmenting ROS generation via NOX and interfering with the VEGF signaling pathway.

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“…Angiogenesis plays a key role in a broad array of physiological and pathological processes (7,10,16). Normal development and maturation of tissues and organs are critically dependent on the establishment and proper function of the vascular system.…”

mentioning

confidence: 99%

Endothelial microparticles affect angiogenesis in vitro: role of oxidative stress

Mezentsev¹,

Merks²,

O’Riordan³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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200

138

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Endothelium-derived microparticles have recently been described as a new marker of endothelial cell dysfunction. Increased levels of circulating microparticles have been documented in inflammatory disorders, diabetes mellitus, and many cardiovascular diseases. Perturbations of angiogenesis play an important role in the pathogenesis of these disorders. We demonstrated previously that isolated endothelial microparticles (EMPs) impair endothelial function in vitro, diminishing acetylcholine-induced vasorelaxation and nitric oxide production by rat aortic rings and simultaneously increasing superoxide production. Herein, using the Matrigel assay of angiogenesis in vitro and a topological analysis of the capillary-like network by human umbilical vein endothelial cells (HUVECs), we investigated the effects of EMPs on formation of the vascular network. All parameters of angiogenesis were affected by treatment for 48 h with isolated EMPs in a concentration of 10(5) but not 10(3) or 10(4) EMPs/ml. The effects included decreases in total capillary length (24%), number of meshes (45%), and branching points (36%) and an increase in mesh area (38%). The positional and topological order indicated that EMPs affect angiogenic parameters uniformly over the capillary network. Treatment with the cell-permeable SOD mimetic Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (Mn-TBAP) partially or completely restored all parameters of angiogenesis affected by EMPs. EMPs reduced cell proliferation rate and increased apoptosis rate in time- and dose-dependent manners, and this phenomenon was also prevented by Mn-TBAP treatment. Our data demonstrate that EMPs have considerable impact on angiogenesis in vitro and may be an important contributor to the pathogenesis of diseases that are accompanied by impaired angiogenesis.

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Coagulation, Fibrinolysis and Angiogenesis: New Insights from Knockout Mice

Cited by 17 publications

References 39 publications

Manipulating angiogenesis in medicine

Manipulating angiogenesis in medicine

Lymphocytic microparticles inhibit angiogenesis by stimulating oxidative stress and negatively regulating VEGF-induced pathways

Endothelial microparticles affect angiogenesis in vitro: role of oxidative stress

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