Endothelial chromosome 13 deletion in congenital heart disease-associated pulmonary arterial hypertension dysregulates SMAD9 signaling.

Supported in part by the National Heart, Lung and Blood Institute of the National Institutes of Health under award numbers R01HL098199, R03HL110831, and RC37HL60917. Author Contributions: K.M.D. and M.A.A. designed the study; acquired, analyzed, and interpreted data; and wrote the manuscript. S.A.C. and S.C.E. acquired samples, established cells, and reviewed the clinical information. R.M.T. reviewed and interpreted the pathology. All authors contributed to writing the manuscript. This letter has an online supplement, which is accessible from this issue's table of contents at www.atsjournals.org Author disclosures are available with the text of this letter at www.atsjournals.org.

[1]  D. Corcoran,et al.  Lesions from patients with sporadic cerebral cavernous malformations harbor somatic mutations in the CCM genes: evidence for a common biochemical pathway for CCM pathogenesis. , 2014, Human molecular genetics.

[2]  M. Gatzoulis,et al.  [Updated clinical classification of pulmonary hypertension]. , 2014, Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir.

[3]  M. Lu,et al.  Coordination of heart and lung co-development by a multipotent cardiopulmonary progenitor , 2013, Nature.

[4]  M. Humbert,et al.  ACVRL1 germinal mosaic with two mutant alleles in hereditary hemorrhagic telangiectasia associated with pulmonary arterial hypertension , 2012, Clinical genetics.

[5]  S. Erzurum,et al.  Somatic Deletion Of SMAD9 In Congenital Heart Disease-Associated Pulmonary Arterial Hypertension Leads To Altered MicroRNA Processing And Cell Hyperproliferation , 2012, ATS 2012.

[6]  B. Dahal,et al.  Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension , 2012, ATS 2012.

[7]  S. Erzurum,et al.  Altered MicroRNA processing in heritable pulmonary arterial hypertension: an important role for Smad-8. , 2011, American journal of respiratory and critical care medicine.

[8]  Graham M Lord,et al.  Molecular genetic characterization of SMAD signaling molecules in pulmonary arterial hypertension , 2011, Human mutation.

[9]  B. Gallie,et al.  Identification of clinically relevant mosaicism in type I hereditary haemorrhagic telangiectasia , 2011, Journal of Medical Genetics.

[10]  P. Bayrak-Toydemir,et al.  Mosaic ACVRL1 and ENG mutations in hereditary haemorrhagic telangiectasia patients , 2011, Journal of Medical Genetics.

[11]  M. Varella‐Garcia,et al.  Somatic chromosome abnormalities in the lungs of patients with pulmonary arterial hypertension. , 2010, American journal of respiratory and critical care medicine.

[12]  G. Raskob,et al.  Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry. , 2010, Chest.

[13]  M. Mullen,et al.  Pulmonary arterial hypertension associated with congenital heart disease , 2009 .

[14]  P. Bayrak-Toydemir,et al.  Multiple sequence variants in hereditary hemorrhagic telangiectasia cases: illustration of complexity in molecular diagnostic interpretation. , 2009, The Journal of molecular diagnostics : JMD.

[15]  P. Jones,et al.  Defective pulmonary vascular remodeling in Smad8 mutant mice. , 2009, Human molecular genetics.

[16]  R. Matsuoka,et al.  A new nonsense mutation of SMAD8 associated with pulmonary arterial hypertension , 2009, Journal of Medical Genetics.

[17]  Ophir D. Klein,et al.  The branching programme of mouse lung development , 2008, Nature.

[18]  A. Moorman,et al.  Role of bone morphogenetic proteins in cardiac differentiation. , 2007, Cardiovascular research.

[19]  J. Knowles,et al.  BMPR2 mutations in pulmonary arterial hypertension with congenital heart disease , 2004, European Respiratory Journal.

[20]  M. Humbert,et al.  Cellular and molecular pathobiology of pulmonary arterial hypertension. , 2004, Journal of the American College of Cardiology.

[21]  L. Rubin,et al.  Primary pulmonary hypertension. , 1997, The New England journal of medicine.

[22]  M. Nehls,et al.  Shear stress inhibits apoptosis of human endothelial cells , 1996, FEBS letters.

[23]  B. Groves,et al.  Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. , 1994, The American journal of pathology.