Molecular and Cellular Mechanisms of Vascular Anomalies

描述（由申请人提供）：该项目名为“血管异常的分子和细胞机制”，代表了三个研究小组（两个在波士顿，一个在比利时布鲁塞尔）的协调和合作努力，以阐明导致皮肤血管异常的原因和异常机制。这些异常通常被称为胎记，包括婴儿血管瘤，在1岁的高加索儿童中发现的5-10%的血管肿瘤，以及血管畸形。血管瘤通常在出生后几天出现，快速生长几周到几个月，然后在5-10年的时间内缓慢消退。在大多数情况下，不需要治疗，但有时至关重要的，结构可能会阻塞或扭曲，造成严重的问题。与血管瘤相反，畸形不会消退，但会随着孩子的成长而成长，并可能危及生命。

DESCRIPTION (provided by applicant): This Program Project, entitled '"Molecular and Cellular Mechanisms of Vascular Anomalies," represents the concerted and collaborative efforts of three research groups, two in Boston and one in Brussels, Belgium, to elucidate the causes and abnormal mechanisms that are responsible for vascular anomalies in the skin. Commonly called birthmarks, these anomalies include infantile hemangioma, a vascular tumor found in 5-10% of Caucasian children at 1 year of age, and vascular malformations. Hemangiomas usually appear a few days after birth, grow rapidly for a few weeks to months, and then slowly regress over a 5-10 year period. In most cases, no treatment is needed, but sometimes vital, structures can be obstructed or distorted causing serious problems. In contrast to hemangiomas, malformations do not regress, but grow with the child, and can become life-threatening. The investigators have recently found that hemangiomas contain clonal expansions of abnormal endothelial cells, and they have discovered two types of mutations that cause localized abnormalities in the skin of patients with venous malformations and glomuvenous malformations. In three research Projects, supported by three Cores, the Program investigators propose to examine and test the hypotheses that hemangiomas result from somatic mutations in genes that control endothelial cell proliferation and/or maturation from precursor cells, causing rapid growth of abnormal capillaries. In addition to identifying such genes and mutations, it is also proposed to identify genes responsible for rare cases of inherited hemangiomas and to establish mouse models allowing further studies of detailed pathological mechanisms. Finally, they now propose to generate mouse models for venous and glomuvenous malformations, characterize the cellular and molecular consequences of the causative mutations, and search for mutations in additional families. The proposed studies should lead to a better understanding of the pathogenesis of hemangiomas and malformations and therefore a basis for development of effective therapies. In addition, a better understanding of the causes and mechanisms of vascular anomalies will provide novel insights into blood vessel formation and growth. This will add significantly to the efforts to develop novel antiangiogenic therapies for cancer, diabetic retinopathy, and rheumatoid arthritis.