Developmental ablation of Id1 and Id3 genes in the vasculature leads to postnatal cardiac phenotypes.
Developmental ablation of Id1 and Id3 genes in the vasculature leads to postnatal cardiac phenotypes.
复制标题
DOI：
10.1016/j.ydbio.2010.10.004
复制
发表时间：
2011-01-01
影响因子：
2.7
通讯作者：
Fraidenraich D
中科院分区：
文献类型：
--
作者：
Zhao Q;Beck AJ;Vitale JM;Schneider JS;Gao S;Chang C;Elson G;Leibovich SJ;Park JY;Tian B;Nam HS;Fraidenraich D
Id 1和Id 3基因在心脏发育过程中起主要作用，尽管它们的表达仅限于非心肌层（内皮细胞-内皮细胞-心外膜）。我们先前描述了Id 1 Id 3双敲除（dKO）小鼠胚胎在妊娠中期死于多种心脏缺陷，但早期致死性排除了Id在出生后心脏中的作用的研究。为了阐明Id基因的出生后作用，我们消融了Id 3基因，并有条件地消融了内皮中的Id 1基因，以产生条件性KO（cKO）胚胎。我们观察了出生时和6个月大时的心脏表型。半数Id cKO小鼠在出生时死亡。出生后死亡与心脏增大、室间隔缺损、小梁形成和脉管系统有关。存活的Id cKO小鼠表现出血管纤维化、心脏增大和心脏功能下降。在Id cKO小鼠的切除皮肤伤口的愈合中也观察到异常的血管反应。在Id cKO心脏中，血管、纤维化和肥大标志物的表达模式发生改变，但加入胰岛素样生长因子结合蛋白-3（IGFbp 3）逆转了血管和纤维化的基因表达谱，但不逆转肥大标志物。因此，血管系统中Id基因的消融导致不同的出生后心脏表型。这些发现提供了重要的见解的作用/s的内皮细胞网络的内皮细胞谱系在心脏疾病的发展，并强调IGFbp 3作为一个潜在的联系Id和它的血管效应。
The Id1 and Id3 genes play major roles during cardiac development, despite their expression being confined to non-myocardial layers (endocardium – endothelium - epicardium). We previously described that Id1Id3 double knockout (dKO) mouse embryos die at mid-gestation from multiple cardiac defects, but early lethality precluded the studies of the roles of Id in the postnatal heart. To elucidate postnatal roles of Id genes, we ablated the Id3 gene and conditionally ablated the Id1 gene in the endothelium to generate conditional KO (cKO) embryos. We observed cardiac phenotypes at birth and at 6 months of age. Half of the Id cKO mice died at birth. Postnatal demise was associated with cardiac enlargement and defects in the ventricular septum, trabeculation and vasculature. Surviving Id cKO mice exhibited fibrotic vasculature, cardiac enlargement and decreased cardiac function. An abnormal vascular response was also observed in the healing of excisional skin wounds of Id cKO mice. Expression patterns of vascular, fibrotic and hypertrophic markers were altered in the Id cKO hearts, but addition of Insulin-Like Growth Factor binding protein-3 (IGFbp3) reversed gene expression profiles of vascular and fibrotic, but not hypertrophic markers. Thus, ablation of Id genes in the vasculature leads to distinct postnatal cardiac phenotypes. These findings provide important insights into the role/s of the endocardial network of the endothelial lineage in the development of cardiac disease, and highlight IGFbp3 as a potential link between Id and its vascular effectors.
登录
查看更多内容
DOI：
10.1158/1078-0432.ccr-08-2362
发表时间：
2010-01-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Lin J;Guan Z;Wang C;Feng L;Zheng Y;Caicedo E;Bearth E;Peng JR;Gaffney P;Ondrey FG
通讯作者：
Ondrey FG
影响因子：
20.1
作者：
Doran AC;Lehtinen AB;Meller N;Lipinski MJ;Slayton RP;Oldham SN;Skaflen MD;Yeboah J;Rich SS;Bowden DW;McNamara CA
通讯作者：
McNamara CA
DOI：
10.1046/j.1440-1681.2002.03655.x
发表时间：
2002-04-01
影响因子：
2.9
作者：
Lehman, JJ;Kelly, DP
通讯作者：
Kelly, DP
影响因子：
64.5
作者：
LIU, JP;BAKER, J;EFSTRATIADIS, A
通讯作者：
EFSTRATIADIS, A
影响因子：
2.7
作者：
Kisanuki, YY;Hammer, RE;Yanagisawa, M
通讯作者：
Yanagisawa, M