ABSTRACT
A angiogênese é produzida por vários fatores conhecidos na atualidade, mas nenhum despertou tanto interesse científico quanto o fator de crescimento vascular endotelial (VEGF). Pode ser expresso em quatrro isoformas codificadas pelo mesmo gene. Sua atividade em humenos é mediada por dois receptores tirosinaquinase KDR e flk-1. A regulaçäo de sua secreçäo e da expressäo dos receptores estäo ligados à hipóxia tecidual, causando vasodilataçäo, aumento da permeabilidade vascular, proliferaçäo das células endoteliais e ativaçäo das metaloproteinases que lisam a matriz extracelular, deixando espaço para o crescimento de um novo vaso. A angiogênese terapêutica age pela esrtimulaçäo do potencial vasculogênico intrínseco à regiäo em isquemia. No coraçäo atua reduzindo a extensäo do infarto, a formaçäo de aneurisma ventricular e melhorando a funçäo ventricular esquerda, aumentando assim a sobrevida do paciente. Esta nova terapia abre novos horizontes para a medicina do terceiro milênio no tratamento de doenças täo antigas quanto o infarto ou qualquer síndrome isquêmica, seja ela aguda ou crônica, contribuindo para melhorar a quelidade de vida e sobrevida desses pacientes.(au)
Subject(s)
Humans , Endothelium, Vascular/cytology , Endothelial Growth Factors , Angiogenesis Inhibitors/physiology , Myocardial Ischemia/therapyABSTRACT
Se presentan los primeros ensayos clínicos de revascularización de extremidades inferiores y del miocardio, mediante el empleo de factores de crecimiento endotelial y fibroblástico. Estos factores se obtienen mediante ingeniería genética. En el caso de las extremidades inferiores se aplica el factor de crecimiento endotelial(VEGF) mediante inyecciones intramusculares en el miembro afectado. En las revascularizaciones miocárdicas se aplicó en 1998 el factor de crecimiento fibroblástico en pacientes que estaban siendo sometidos a cirugía de by-pass. Un año después se empleó el factor de crecimiento endotelial en inyecciones directas al miocardio a través de una mini toracotomía. Finalmente, en el año 2000 se aplica el factor de crecimiento fibroblástico, mediante coronariografía. Se analizan las complicaciones y rendimiento de la técnica intracoronaria la que se visualiza como una esperanza en el futuro de los pacientes coronarios
Subject(s)
Humans , Angiogenesis Inhibitors/physiology , Neovascularization, Physiologic/physiology , Endothelial Growth Factors , Fibroblast Growth FactorsSubject(s)
Humans , Animals , Collateral Circulation/physiology , Coronary Disease/therapy , Genetic Therapy , Myocardial Ischemia/therapy , Neovascularization, Physiologic , Atherosclerosis , Coronary Vessels , Dogs , Endothelial Growth Factors/physiology , Fibroblast Growth Factors/physiology , Angiogenesis Inhibitors/physiology , Mice , Neoplasm Metastasis/drug therapy , Neovascularization, Physiologic/physiology , Plasmids/therapeutic use , Recombinant Proteins/metabolism , SwineABSTRACT
Endothelial cell proliferation and differentiation into blood capillaries (i.e., angiogenesis) are essential for growth and development, wound healing, osetogenesis, etc. But abnormal angiogenesis during tumor progression could lead to serious consequences. Angiogenesis is a complex biochemical process, and is often difficult to study the molecular mechanism in vivo due to interference by multitude of factors. Here, I present a non-transformed capillary endothelial cell line as a model which has been extensively characterized morphologically and biochemically to study the fundamentals of the angiogenic process. Studies completed in our laboratory also evidenced that expression of Glc3Man9GlcNAc2-PP-Dol is intricately connected with the balance between the cellular proliferation and apoptosis during angiogenesis.
Subject(s)
Humans , Animals , Cattle , Female , Mice , Adult , Capillaries/cytology , Endothelium, Vascular/cytology , Angiogenesis Inhibitors/physiology , Models, Biological , Neovascularization, Physiologic/physiology , Apoptosis , Capillaries/metabolism , Catecholamines/metabolism , Cell Division , Collateral Circulation , Culture Media , Dolichols/metabolism , Endothelial Growth Factors/metabolism , Endothelial Growth Factors/physiology , Endothelium, Vascular/metabolism , Gene Expression , Glycoproteins/genetics , Glycoproteins/metabolism , Glycosylation , Homeostasis , Immunohistochemistry , Angiogenesis Inhibitors/genetics , Neovascularization, Physiologic/genetics , Phenotype , Receptors, Adrenergic, beta/physiology , Research , Growth Substances/physiology , Time FactorsSubject(s)
Humans , Carcinoma, Basal Cell/genetics , /adverse effects , Carcinoma, Basal Cell/immunology , Carcinoma, Basal Cell/secondary , Chromosomes, Human, Pair 9 , Angiogenesis Inhibitors/physiology , Basal Cell Nevus Syndrome/diagnosis , Basal Cell Nevus Syndrome/pathology , Telomerase/physiologyABSTRACT
Angiogenesis, the sprouting of new blood vessels from pre-existing vessels, is a complex, multicellular phenomenon involving capillary endothelial cell (EC) proliferation, migration, and tissue infiltration. The elucidation of the biochemical and molecular factors which control angiogenesis is fundamental to our understanding of normal blood vessel development, as well as of the pathogenesis of abnormal blood vessel formation. Angiogenesis is associated with numerous physiological processes, including embryogenesis, wound healing, organ regeneration, and the female reproductive cycle. However, abnormal angiogenesis also plays a major role in the pathogenesis of tumor growth, rheumatoid arthritis, atherosclerosis and various retinopathies. The cellular and molecular mechanisms underlying both physiological and pathophysiological angiogenesis are only now beginning to be understood. Vascular endothelial growth factor was initially discovered as an unidentified tumor-derived factor which increased microvascular permeability (vascular permeability factor, VPF). Subsequently, it was determined that the protein exhibited mitogenic effects on endothelial cells, but not other cell types. Multiple receptor subtypes have been described which may in part explain the multiplicity of biological actions that have been ascribed to VEGF/VPF in the literature. In this overview, we briefly summarize what is currently known about VEGF and VEGF receptor biology, as well as VEGF receptor signal transduction mechanisms in endothelial cells