Dosage-dependent requirement of BNW type II receptor for maintenance of vascular integrity
Dosage-dependent requirement of BNW type II receptor for maintenance of vascular integrity
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DOI：
10.1182/blood-2006-11-058594
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发表时间：
2007-09-01
期刊：
影响因子：
20.3
通讯作者：
Li, En
中科院分区：
文献类型：
--
作者：
Liu, Dong;Wang, Jian;Li, En
Germ-line mutations in bone morphogenic protein type 11 receptor (Bmpr2) confer susceptibility to pulmonary arterial hypertension (PAH), which is characterized by obstructive vascular lesions in small arteries. The molecular and cellular mechanisms that account for the etiology of this disorder remain elusive, as does the role of Bmpr2 in postnatal tissue homeostasis. Here we show that in adult mice, stably silencing Bmpr2 expression by RNA interference does not increase pulmonary arterial resistance but results in severe mucosal hemorrhage, incomplete mural cell coverage on vessel walls, and gastrointestinal hyperplasla. We present evidence that BMP receptor signaling regulates vascular remodeling during angiogenesis by maintaining the expression of endothelial guidance molecules that promote vessel patterning and maturation and by counteracting growth factor-induced AKT activation. Attenuation of this function may cause vascular dysmorphogenesis and predisposition to angioproliferative diseases. Our findings provide a mechanistic link between PAH and other diseases associated with the BMP/TGF-beta pathways, such as hereditary hemorrhagic telanglectasia and juvenile polyposis syndrome.
