Global S&T Development Trend Analysis Platform of Resources and Environment
DOI | 10.1038/s41467-017-01307-8 |
Aortic pathology from protein kinase G activation is prevented by an antioxidant vitamin B-12 analog | |
Schwaerzer, Gerburg K.1; Kalyanaraman, Hema1; Casteel, Darren E.1; Dalton, Nancy D.1; Gu, Yusu1; Lee, Seunghoe1; Zhuang, Shunhui1; Wahwah, Nisreen1; Schilling, Jan M.2; Patel, Hemal H.2; Zhang, Qian1; Makino, Ayako1; Milewicz, Dianna M.3; Peterson, Kirk L.1; Boss, Gerry R.1; Pilz, Renate B.1 | |
2019-08-06 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | USA |
英文摘要 | People heterozygous for an activating mutation in protein kinase G1 (PRKG1, p.Arg177GIn) develop thoracic aortic aneurysms and dissections (TAAD) as young adults. Here we report that mice heterozygous for the mutation have a three-fold increase in basal protein kinase G (PKG) activity, and develop age-dependent aortic dilation. Prkg1(R177Q/+) aortas show increased smooth muscle cell apoptosis, elastin fiber breaks, and oxidative stress compared to aortas from wild type littermates. Transverse aortic constriction (TAC)-to increase wall stress in the ascending aorta-induces severe aortic pathology and mortality from aortic rupture in young mutant mice. The free radical-neutralizing vitamin B-12-analog cobinamide completely prevents age-related aortic wall degeneration, and the unrelated anti-oxidant N-acetylcysteine ameliorates TAC-induced pathology. Thus, increased basal PKG activity induces oxidative stress in the aorta, raising concern about the widespread clinical use of PKG-activating drugs. Cobinamide could be a treatment for aortic aneurysms where oxidative stress contributes to the disease, including Marfan syndrome. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000478867500018 |
WOS关键词 | SMOOTH-MUSCLE-CELLS ; NADPH OXIDASE 4 ; REACTIVE OXYGEN ; OXIDATIVE STRESS ; NITRIC-OXIDE ; CYCLIC-GMP ; TGF-BETA ; I-ALPHA ; ANEURYSM PROGRESSION ; ANGIOTENSIN-II |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203524 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA; 2.Univ Calif San Diego, Dept Anesthesiol, La Jolla, CA 92093 USA; 3.Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Div Med Genet & Cardiol, Houston, TX 77030 USA |
推荐引用方式 GB/T 7714 | Schwaerzer, Gerburg K.,Kalyanaraman, Hema,Casteel, Darren E.,et al. Aortic pathology from protein kinase G activation is prevented by an antioxidant vitamin B-12 analog[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Schwaerzer, Gerburg K..,Kalyanaraman, Hema.,Casteel, Darren E..,Dalton, Nancy D..,Gu, Yusu.,...&Pilz, Renate B..(2019).Aortic pathology from protein kinase G activation is prevented by an antioxidant vitamin B-12 analog.NATURE COMMUNICATIONS,10. |
MLA | Schwaerzer, Gerburg K.,et al."Aortic pathology from protein kinase G activation is prevented by an antioxidant vitamin B-12 analog".NATURE COMMUNICATIONS 10(2019). |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论