RESUMO
OBJECTIVE: The concept of vascular pruning, the "cuting-off" of vessels, is gaining importance due to expansion of angio-modulating therapies. The proangiogenic effects of vascular endothelial growth factor (VEGF) are broadly described, but the mechanisms of structural alterations by its downregulation are not known. METHODS AND RESULTS: VEGF(165)-releasing hydrogels were applied onto the chick chorioallantoic membrane on embryonic day 10. The hydrogels, designed to completely degrade within 2 days, caused high-level VEGF presentation followed by abrupt VEGF withdrawal. Application of VEGF resulted in a pronounced angiogenic response within 24 hours. The drastic decrease in level of exogenous VEGF-A within 48 hours was corroborated by enzyme-linked immunosorbent assay. Following this VEGF withdrawal we observed vasculature adaptation by means of intussusception, including intussusceptive vascular pruning. As revealed on vascular casts and serial semithin sections, intussusceptive vascular pruning occurred by emergence of multiple eccentric pillars at bifurcations. Time-lapse in vivo microscopy has confirmed the de novo occurrence of transluminal pillars and their capability to induce pruning. Quantitative evaluation corroborated an extensive activation of intussusception associated with VEGF withdrawal. CONCLUSIONS: Diminution of VEGF level induces vascular tree regression by intussusceptive vascular pruning. This observation may allude to the mechanism underlying the "normalization" of tumor vasculature if treated with antiangiogenic drugs. The mechanism described here gives new insights into the understanding of the processes of vasculature regression and hence provides new and potentially viable targets for antiangiogenic and/or angio-modulating therapies during various pathological processes.
Assuntos
Membrana Corioalantoide/irrigação sanguínea , Neovascularização Fisiológica/fisiologia , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/deficiência , Animais , Apoptose/fisiologia , Embrião de Galinha , Endotélio Vascular/patologia , Endotélio Vascular/fisiologia , Regulação da Expressão Gênica/fisiologia , Modelos Animais , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/genética , Transdução de Sinais/genética , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
Falls in the elderly are common with consecutive high mortality and morbidity. Recent consecutive data focus on identification and therapy of intrinsic risk factors. Sarcopenia, imbalance and gait disorders represent the major risk factors. Sarcopenia is caused by a disequilibrium of protein synthesis and breakdown, probably in consequence of age-related changes in protein metabolism. Protein supplements in combination with strength training shows the best benefit. Disorders in balance and gait are caused by age-related or pathologic changes in a complex regulation system of gait. The individual fall risk correlates with the gait variability and even increases with bad dual task performance. Activities with high requirements of attention and body awareness are the most effective prevention for falls in the elderly (-50%).
Les chutes chez les personnes âgées sont fréquentes et entraînent un fort taux de morbidité et de mortalité. Les récentes études se sont focalisées sur l'identification et les traitements des facteurs de risques. La sarcopénie, les troubles de la marche et de l'équilibre constituent les facteurs de risques majeurs. La sarcopénie ou faiblesse musculaire résulte d'un déséquilibre entre la synthèse et la dégradation des protéines, conséquence de la modification du métabolisme liée à l'âge. Un apport supplémentaire en protéines combiné à un renforcement musculaire apporte les meilleurs résultats. Les troubles de l'équilibre et de la marche sont liés à l'âge ou à des pathologies touchant les systèmes complexes de régulation de la marche. Le risque individuel de chute est en corrélation avec les variabilités de la marche et augmente dans les situations où il faut accomplir une double tâche. Les activités, requérant une forte concentration, une bonne connaissance et maîtrise de son corps, constituent la prévention la plus efficace contre les chutes chez la personne âgée.