PDE3A mutations cause autosomal dominant hypertension with brachydactyly
文献类型：期刊论文
| 作者 | Maass, Philipp G.1,2; Aydin, Atakan1,2; Luft, Friedrich C.1,2,3; Schaechterle, Carolin2; Weise, Anja4; Stricker, Sigmar5,6; Lindschau, Carsten7,8; Vaegler, Martin1,2,9; Qadri, Fatimunnisa1,2; Toka, Hakan R.1,10,11 |
| 刊名 | NATURE GENETICS
 |
| 出版日期 | 2015-06-01 |
| 卷号 | 47期号:6页码:647-653 |
| ISSN号 | 1061-4036 |
| 英文摘要 | Cardiovascular disease is the most common cause of death worldwide, and hypertension is the major risk factor(1). Mendelian hypertension elucidates mechanisms of blood pressure regulation. Here we report six missense mutations in PDE3A (encoding phosphodiesterase 3A) in six unrelated families with mendelian hypertension and brachydactyly type E (HTNB)(2). The syndrome features brachydactyly type E (BDE), severe salt-independent but age-dependent hypertension, an increased fibroblast growth rate, neurovascular contact at the rostral-ventrolateral medulla, altered baroreflex blood pressure regulation and death from stroke before age 50 years when untreated(3,4). In vitro analyses of mesenchymal stem cell-derived vascular smooth muscle cells (VSMCs) and chondrocytes provided insights into molecular pathogenesis. The mutations increased protein kinase A-mediated PDE3A phosphorylation and resulted in gain of function, with increased cAMP-hydrolytic activity and enhanced cell proliferation. Levels of phosphorylated VASP were diminished, and PTHrP levels were dysregulated. We suggest that the identified PDE3A mutations cause the syndrome. VSMC-expressed PDE3A deserves scrutiny as a therapeutic target for the treatment of hypertension. |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000355386500017 |
| 源URL | [http://ir.psych.ac.cn/handle/311026/13368]  |
| 专题 | 心理研究所_健康与遗传心理学研究室 |
| 作者单位 | 1.Joint Cooperat Charite Med Fac, ECRC, Berlin, Germany 2.Helmholtz Assoc MDC, Max Delbruck Ctr Mol Med, Berlin, Germany 3.Vanderbilt Univ, Sch Med, Dept Med, Div Clin Pharmacol, Nashville, TN 37212 USA 4.Univ Jena, Jena Univ Hosp, Inst Human Genet, Jena, Germany 5.Max Planck Inst Mol Genet, D-14195 Berlin, Germany 6.Free Univ Berlin, Inst Chem & Biochem, Berlin, Germany 7.Leibniz Univ Hannover, Sch Med, Dept Nephrol, D-30167 Hannover, Germany 8.Staatl Technikerschule Berlin, Berlin, Germany 9.Univ Tubingen, Dept Urol, Lab Tissue Engn, Tubingen, Germany 10.Eastern Virginia Med Sch, Div Nephrol & Hypertens, Norfolk, VA 23501 USA |
| 推荐引用方式 GB/T 7714 | Maass, Philipp G.,Aydin, Atakan,Luft, Friedrich C.,et al. PDE3A mutations cause autosomal dominant hypertension with brachydactyly[J]. NATURE GENETICS,2015,47(6):647-653. |
| APA | Maass, Philipp G..,Aydin, Atakan.,Luft, Friedrich C..,Schaechterle, Carolin.,Weise, Anja.,...&Baehring, Sylvia.(2015).PDE3A mutations cause autosomal dominant hypertension with brachydactyly.NATURE GENETICS,47(6),647-653. |
| MLA | Maass, Philipp G.,et al."PDE3A mutations cause autosomal dominant hypertension with brachydactyly".NATURE GENETICS 47.6(2015):647-653. |
入库方式： OAI收割
来源：心理研究所
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