PDE3A mutations cause autosomal dominant hypertension with brachydactyly | |
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; Schulz, Herbert2,12; Krawitz, Peter M.5,13,14; Parkhomchuk, Dmitri13,14; Hecht, Jochen14; Hollfinger, Irene2; Wefeld-Neuenfeld, Yvette2; Bartels-Klein, Eireen2; Muehl, Astrid2; Kann, Martin15,16; Schuster, Herbert17; Chitayat, David18,19; Bialer, Martin G.20,21; Wienker, Thomas F.22; Ott, Juerg23,24; Rittscher, Katharina4; Liehr, Thomas4; Jordan, Jens25; Plessis, Ghislaine26; Tank, Jens25; Mai, Knut1,2; Naraghi, Ramin27; Hodge, Russell; Hopp, Maxwell28; Hattenbach, Lars O.29; Busjahn, Andreas30; Rauch, Anita31; Vandeput, Fabrice32,33,34; Gong, Maolian1,2; Rueschendorf, Franz; Huebner, Norbert2,36; Haller, Hermann7; Mundlos, Stefan5,13,14; Bilginturan, Nihat37; Movsesian, Matthew A.32,33,34; Klussmann, Enno2,35; Toka, Okan38; Baehring, Sylvia1,2 | |
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. |
2015-06-01 | |
语种 | 英语 |
发表期刊 | NATURE GENETICS |
ISSN | 1061-4036 |
卷号 | 47期号:6页码:647-653 |
期刊论文类型 | Article |
收录类别 | SCI |
WOS记录号 | WOS:000355386500017 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.psych.ac.cn/handle/311026/13368 |
专题 | 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 11.Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA 12.Univ Cologne, CCG, D-50931 Cologne, Germany 13.Charite, Inst Med Genet & Human Genet, D-13353 Berlin, Germany 14.Charite, Berlin Brandenburg Ctr Regenerat Therapies BCRT, D-13353 Berlin, Germany 15.Univ Cologne, Dept Med 2, D-50931 Cologne, Germany 16.Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany 17.INFOGEN, Berlin, Germany 18.Univ Toronto, Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada 19.Univ Toronto, Mt Sinai Hosp, Dept Obstet & Gynecol, Prenatal Diag & Med Genet Program, Toronto, ON M5G 1X5, Canada 20.North Shore LIJ Hlth Syst, Div Med Genet, Manhasset, NY USA 21.North Shore LIJ Hlth Syst, Dept Pediat, Manhasset, NY USA 22.Univ Bonn, Inst Med Biometry Informat & Epidemiol, Bonn, Germany 23.Chinese Acad Sci, Inst Psychol, Beijing 100101, Peoples R China 24.Rockefeller Univ, Stat Genet, New York, NY 10021 USA 25.Hannover Med Sch, Inst Clin Pharmacol, Hannover, Germany 26.CHU Caen, Cytogenet Postnatale & Genet Clin, F-14000 Caen, France 27.Bundeswehrkrankenhaus Ulm, Dept Neurosurg, Ulm, Germany 28.Griffith Base Hosp, Dept Pediat, Griffith, NSW, Australia 29.Hosp Ludwigshafen, Dept Ophthalmol, Ludwigshafen, Germany 30.HealthTwist, Berlin, Germany 31.Univ Zurich, Inst Med Genet, Zurich, Switzerland 32.Vet Affairs Salt Lake City Hlth Care Syst, Cardiol Sect, Salt Lake City, UT USA 33.Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA 34.Univ Utah, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA 35.DZHK German Ctr Cardiovasc Res, Berlin, Germany 36.Charite, D-13353 Berlin, Germany 37.Hacettepe Univ, Dept Pediat Oncol, Ankara, Turkey 38.Univ Erlangen Nurnberg, Childrens Hosp, Dept Pediat Cardiol, D-91054 Erlangen, Germany |
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. |
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