Essential Role of Endothelial Smad4 in Vascular Remodeling and Integrity Export

@article{citeulike:2742751, abstract = {New blood vessels are formed through the assembly or sprouting of endothelial cells (ECs) and become stabilized by the formation of perivascular matrix and the association with supporting mural cells. To investigate the role of endothelial Smad4 in vascular development, we deleted the Smad4 gene specifically in ECs using the Cre-LoxP system. EC-specific Smad4 mutant mice died at embryonic day 10.5 due to cardiovascular defects, including attenuated vessels sprouting and remodeling, collapsed dorsal aortas, enlarged hearts with reduced trabeculae, and failed endocardial cushion formation. Noticeably, Smad4-deficient ECs demonstrated an intrinsic defect in tube formation in vitro. Furthermore, the mutant vascular ECs dissociated away from the surrounding cells and suffered from impaired development of vascular smooth muscle cells. The disturbed vascular integrity and maturation was associated with aberrant expression of angiopoietins and a gap junction component, connexin43. Collectively, we have provided direct functional evidence that Smad4 activity in the developing ECs is essential for blood vessel remodeling, maturation, and integrity. 10.1128/MCB.00577-07}, author = {Lan, Yu and Liu, Bing and Yao, Huiyu and Li, Fangfei and Weng, Tujun and Yang, Guan and Li, Wenlong and Cheng, Xuan and Mao, Ning and Yang, Xiao}, citeulike-article-id = {2742751}, citeulike-linkout-0 = {http://dx.doi.org/10.1128/MCB.00577-07}, citeulike-linkout-1 = {http://mcb.asm.org/cgi/content/abstract/27/21/7683}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17724086}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17724086}, day = {1}, doi = {10.1128/MCB.00577-07}, journal = {Mol. Cell. Biol.}, keywords = {conditional\_ko, cre, embryo, endothelial\_phenotype, mouse, smad4}, month = {November}, number = {21}, pages = {7683--7692}, posted-at = {2008-05-01 15:09:58}, priority = {2}, title = {Essential Role of Endothelial Smad4 in Vascular Remodeling and Integrity}, url = {http://dx.doi.org/10.1128/MCB.00577-07}, volume = {27}, year = {2007} }

TY - JOUR ID - citeulike:2742751 L3 - citeulike-article-id:2742751 N2 - New blood vessels are formed through the assembly or sprouting of endothelial cells (ECs) and become stabilized by the formation of perivascular matrix and the association with supporting mural cells. To investigate the role of endothelial Smad4 in vascular development, we deleted the Smad4 gene specifically in ECs using the Cre-LoxP system. EC-specific Smad4 mutant mice died at embryonic day 10.5 due to cardiovascular defects, including attenuated vessels sprouting and remodeling, collapsed dorsal aortas, enlarged hearts with reduced trabeculae, and failed endocardial cushion formation. Noticeably, Smad4-deficient ECs demonstrated an intrinsic defect in tube formation in vitro. Furthermore, the mutant vascular ECs dissociated away from the surrounding cells and suffered from impaired development of vascular smooth muscle cells. The disturbed vascular integrity and maturation was associated with aberrant expression of angiopoietins and a gap junction component, connexin43. Collectively, we have provided direct functional evidence that Smad4 activity in the developing ECs is essential for blood vessel remodeling, maturation, and integrity. 10.1128/MCB.00577-07 IS - 21 JF - Mol. Cell. Biol. EP - 7692 TI - Essential Role of Endothelial Smad4 in Vascular Remodeling and Integrity VL - 27 SP - 7683 KW - conditional_ko KW - cre KW - embryo KW - endothelial_phenotype KW - mouse KW - smad4 AU - Lan, Yu AU - Liu, Bing AU - Yao, Huiyu AU - Li, Fangfei AU - Weng, Tujun AU - Yang, Guan AU - Li, Wenlong AU - Cheng, Xuan AU - Mao, Ning AU - Yang, Xiao PY - 2007/11/01/ UR - http://dx.doi.org/10.1128/MCB.00577-07 ER -