IR@PKUHSC  > 北京大学第二临床医学院  > 血管外科
学科主题临床医学
Tgfbr2 disruption in postnatal smooth muscle impairs aortic wall homeostasis
Li, Wei1,2,3; Li, Qingle1,2,3; Jiao, Yang1,2; Qin, Lingfeng1,2; Ali, Rahmat1,2; Zhou, Jing1,2; Ferruzzi, Jacopo4,5; Kim, Richard W.1,2; Geirsson, Arnar1,2,6; Dietz, Harry C.7; Offermanns, Stefan8; Humphrey, Jay D.4,5; Tellides, George1,2,6
刊名JOURNAL OF CLINICAL INVESTIGATION
2014-02-01
DOI10.1172/JCI69942
124期:2页:755-767
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Medicine, Research & Experimental
研究领域[WOS]Research & Experimental Medicine
关键词[WOS]GROWTH-FACTOR-BETA ; MARFAN-SYNDROME ; ANGIOTENSIN-II ; ANEURYSM PROGRESSION ; ALPHA-ACTIN ; MUTATIONS ; ACTIVATION ; CELLS ; MICE ; PATHOGENESIS
英文摘要

TGF-beta is essential for vascular development; however, excess TGF-beta signaling promotes thoracic aortic aneurysm and dissection in multiple disorders, including Marfan syndrome. Since the pathology of TGF-beta overactivity manifests primarily within the arterial media, it is widely assumed that suppression of TGF-beta signaling in vascular smooth muscle cells will ameliorate aortic disease. We tested this hypothesis by conditional inactivation of Tgfbr2, which encodes the TGF-beta type II receptor, in smooth muscle cells of postweanling mice. Surprisingly, the thoracic aorta rapidly thickened, dilated, and dissected in these animals. Tgfbr2 disruption predictably decreased canonical Smad signaling, but unexpectedly increased MAPK signaling. Type II receptor-independent effects of TGF-beta and pathological responses by nonrecombined smooth muscle cells were excluded by serologic neutralization. Aortic disease was caused by a perturbed contractile apparatus in medial cells and growth factor production by adventitial cells, both of which resulted in maladaptive paracrine interactions between the vessel wall compartments. Treatment with rapamycin restored a quiescent smooth muscle phenotype and prevented dissection. Tgfbr2 disruption in smooth muscle cells also accelerated aneurysm growth in a murine model of Marfan syndrome. Our data indicate that basal TGF-beta signaling in smooth muscle promotes postnatal aortic wall homeostasis and impedes disease progression.

语种英语
WOS记录号WOS:000331413300034
引用统计
被引频次:74[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66286
专题北京大学第二临床医学院_血管外科
作者单位1.Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA
2.Yale Univ, Dept Biomed Engn, New Haven, CT USA
3.Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA
4.Yale Univ, Sch Med, Interdept Program Vasc Biol & Therapeut, New Haven, CT 06510 USA
5.Peking Univ Peoples Hosp, Dept Vasc Surg, Beijing, Peoples R China
6.Yale Univ, Interdept Program Vasc Biol & Therapeut, New Haven, CT USA
7.Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA
8.Max Planck Inst Heart & Lung Res, Dept Pharmacol, Bad Nauheim, Germany
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GB/T 7714
Li, Wei,Li, Qingle,Jiao, Yang,et al. Tgfbr2 disruption in postnatal smooth muscle impairs aortic wall homeostasis[J]. JOURNAL OF CLINICAL INVESTIGATION,2014,124(2):755-767.
APA Li, Wei.,Li, Qingle.,Jiao, Yang.,Qin, Lingfeng.,Ali, Rahmat.,...&Tellides, George.(2014).Tgfbr2 disruption in postnatal smooth muscle impairs aortic wall homeostasis.JOURNAL OF CLINICAL INVESTIGATION,124(2),755-767.
MLA Li, Wei,et al."Tgfbr2 disruption in postnatal smooth muscle impairs aortic wall homeostasis".JOURNAL OF CLINICAL INVESTIGATION 124.2(2014):755-767.
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