SCCOR in Thoracic Aortic Aneurysms and Dissections

Summary

Principal Investigator: Dianna Milewicz
Affiliation: Texas Medical Center
Country: USA
Abstract: Thoracic aortic disease is the fifteenth leading cause of death in the United States, with aortic dissections being the thirteenth leading cause of death for individuals between the ages of 55 and 64 years. The major manifestations of disease affecting the aorta in the thoracic cavity are aneurysms and dissections. The theme of the application, "Specialized Center for Clinically Oriented Research in Thoracic Aortic Aneurysms and Dissections" (SCCOR-TAAD), is to improve our understanding of the pathogenesis of these diseases in hopes of developing better methods to diagnose, treat, and predict outcome of thoracic aortic disease with the ultimate goal of preventing premature deaths. Project 1, Dysregulation of TGF(3 signaling in aortic aneurysms and dissections, Dianna Milewicz, M.D. Ph.D. Project Leader, focuses on elucidating the role that dysregulation of TGF-p signaling plays in both familial and non-familial cases of thoracic aortic aneurysms and dissections. Project 2, Apoptosis of Smooth Muscle Cells in Aortic Aneurysms, Yong-Jian Geng, M.D. Ph.D. Project Leader, addresses accelerated apoptosis of vascular cells as a major pathological change in the development of thoracic aortic aneurysms and dissections. Project 3, Inflammatory Biomarkers of Aortic Aneurysms, Allan Brasier, M.D. Project Leader, focuses on elucidating the role of angiotensin II (Ang II)- induced inflammation in aortic aneurysms. Project 4, Predictors of Outcomes after Acute Aortic Dissection, Chul Ahn, Ph.D., Project Leader, will explore the hypothesis that there are clinical, socioeconomic, genetic, and plasma markers that will predict which individuals will have an adverse outcome after an acute dissection. Project 5, Genetic Determinants of Thoracic Aortic Aneurysms and Dissections, Xing Li Wang, M.D., Ph.D. Project Leader, will explore the hypothesis that genetic variants contribute significantly to sporadic thoracic aortic aneurysms and dissections. Project 6, Computerized Ultrasound/MR Imaging for Thoracic Aortic Aneurysms and Dissections, Jeff Towbin, M.D. Project Leader, is focused on improving the ability to detect aortic disease using ultrasound and MRI. The proposed SCCOR-TAAD has been established to take advantage of the considerable clinical expertise, patient population, research talent and established centers in the Texas Medical Center, and represents a comprehensive research approach to understand the pathology, identify biomarkers that predict progression and outcome, and improve the methods to diagnose thoracic aortic disease.
Funding Period: 2006-05-05 - 2011-04-30
more information: NIH RePORT

Top Publications

  1. pmc Apolipoprotein-J prevention of fetal cardiac myoblast apoptosis induced by ethanol
    Yangxin Li
    Texas Heart Institute and The University of Texas Health Science Center, Houston, TX 77030, USA
    Biochem Biophys Res Commun 357:157-61. 2007
  2. doi An FBN1 pseudoexon mutation in a patient with Marfan syndrome: confirmation of cryptic mutations leading to disease
    Dong Chuan Guo
    The Department of Internal Medicine, The University of Texas Medical School at Houston, 6431 Fannin, MSB 6 100, Houston, TX 77030, USA
    J Hum Genet 53:1007-11. 2008
  3. doi Ascending and transverse aortic arch repair: the impact of retrograde cerebral perfusion
    Anthony L Estrera
    Department of Cardiothoracic and Vascular Surgery, The University of Texas Houston Medical School, 6410 Fannin, Suite 425, Houston, TX 77030, USA
    Circulation 118:S160-6. 2008
  4. pmc Characterization of the inflammatory cells in ascending thoracic aortic aneurysms in patients with Marfan syndrome, familial thoracic aortic aneurysms, and sporadic aneurysms
    Rumin He
    Department of Internal Medicine, The University of Texas Medical School at Houston, Houston, Texas 77030, USA
    J Thorac Cardiovasc Surg 136:922-9, 929.e1. 2008
  5. pmc Phospho-control of TGF-beta superfamily signaling
    Katharine H Wrighton
    Michael E DeBakey Department of Surgery, Department of Molecular and Cellular Biology and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
    Cell Res 19:8-20. 2009
  6. pmc Transforming Growth Factor {beta} Can Stimulate Smad1 Phosphorylation Independently of Bone Morphogenic Protein Receptors
    Katharine H Wrighton
    Michael E DeBakey Department of Surgery and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 284:9755-63. 2009
  7. doi Serum myoglobin and renal morbidity and mortality following thoracic and thoraco-abdominal aortic repair: does rhabdomyolysis play a role?
    C C Miller
    Department of Cardiothoracic and Vascular Surgery, University of Texas Medical School at Houston, Memorial Hermann Heart and Vascular Institute, Houston, TX 77030, USA
    Eur J Vasc Endovasc Surg 37:388-94. 2009
  8. pmc Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease
    Dong Chuan Guo
    The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
    Am J Hum Genet 84:617-27. 2009
  9. doi Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations
    V Tran-Fadulu
    Department of Internal Medicine and Department of Neurosurgery, University of Texas Health Science Center at Houston, Texas, USA
    J Med Genet 46:607-13. 2009
  10. doi Cerebrospinal fluid drainage during thoracic aortic repair: safety and current management
    Anthony L Estrera
    Department of Cardiothoracic and Vascular Surgery, University of Texas Medical School Houston, Houston, Texas, USA
    Ann Thorac Surg 88:9-15; discussion 15. 2009

Scientific Experts

  • Anthony Estrera
  • C C Miller
  • Allan Brasier
  • Dianna Milewicz
  • Dong Chuan Guo
  • Katharine H Wrighton
  • Ming Xiang Zhang
  • Joseph S Coselli
  • Hazim J Safi
  • Cheng Zhang
  • Scott A LeMaire
  • Xin Hua Feng
  • Yun Zhang
  • Van Tran-Fadulu
  • L Maximilian Buja
  • Xiao Nan Li
  • Christina L Papke
  • Ying H Shen
  • Xing Li Wang
  • Ariel Brautbar
  • V Tran-Fadulu
  • Xia Lin
  • Brian C Tieu
  • Dong H Kim
  • Jian Wang
  • Elizabeth Sparks
  • Hariyadarshi Pannu
  • Pallav J Shah
  • Elizabeth Pretzer
  • Sanjay S Shete
  • Nili Avidan
  • C S Raman
  • Robert K Yu
  • Rumin He
  • Chul Ahn
  • Yong Jian Geng
  • Yangxin Li
  • Sanjeev Choudhary
  • Luis M Franco
  • John W Belmont
  • P H Byers
  • G W Vick
  • S Smart
  • Reed E Pyeritz
  • C Ahn
  • Heidi Spratt
  • Adrian Recinos
  • C M Lonsford
  • James T Willerson
  • Marcia C Willing
  • Xiaoxi Ju
  • C Boccalandro
  • ERIC A BOERWINKLE
  • H Pannu
  • Sudha Veeraraghavan
  • A L Lafont
  • James C Grotta
  • Michael N Singh
  • Donna M Muzny
  • D H Kim
  • Ellen S Regalado
  • Chang Lee
  • Steven E Scherer
  • Wanda Lejeune
  • Lorraine Q Frazier
  • Ronald L Dalman
  • Paul B Yu
  • Ralph Jay Johnson
  • J S Coselli
  • K L Peterson
  • Ali J Marian
  • Ronald G Tilton
  • S A Lemaire
  • David A Wheeler
  • Hong Sun
  • J Zenger Hain
  • M C Willing
  • Adel D Irani
  • Taek Yeon Lee
  • Senthil Duraisamy
  • Magalie S Leduc
  • Koichi Yoshimura
  • Prateek Gupta
  • Riad Meada
  • Jingwu Zhang
  • Liang Chen
  • Joseph Coselli
  • Feng shuang An
  • Jared K Burks
  • Wei Sun

Detail Information

Publications26

  1. pmc Apolipoprotein-J prevention of fetal cardiac myoblast apoptosis induced by ethanol
    Yangxin Li
    Texas Heart Institute and The University of Texas Health Science Center, Houston, TX 77030, USA
    Biochem Biophys Res Commun 357:157-61. 2007
    ..Thus, ApoJ serves as a cytoprotective protein that protects cardiac stem cells against EtOH cytotoxicity...
  2. doi An FBN1 pseudoexon mutation in a patient with Marfan syndrome: confirmation of cryptic mutations leading to disease
    Dong Chuan Guo
    The Department of Internal Medicine, The University of Texas Medical School at Houston, 6431 Fannin, MSB 6 100, Houston, TX 77030, USA
    J Hum Genet 53:1007-11. 2008
    ..Identification of a novel pseudoexon mutation in FBN1, in association with a clinical diagnosis of MFS, confirms that cryptic mutations that are missed by the current DNA-based diagnostic methods have a causative role...
  3. doi Ascending and transverse aortic arch repair: the impact of retrograde cerebral perfusion
    Anthony L Estrera
    Department of Cardiothoracic and Vascular Surgery, The University of Texas Houston Medical School, 6410 Fannin, Suite 425, Houston, TX 77030, USA
    Circulation 118:S160-6. 2008
    ..We examined our experience with ascending and transverse arch repairs to determine the impact of retrograde cerebral perfusion on stroke and mortality...
  4. pmc Characterization of the inflammatory cells in ascending thoracic aortic aneurysms in patients with Marfan syndrome, familial thoracic aortic aneurysms, and sporadic aneurysms
    Rumin He
    Department of Internal Medicine, The University of Texas Medical School at Houston, Houston, Texas 77030, USA
    J Thorac Cardiovasc Surg 136:922-9, 929.e1. 2008
    ..This study sought to characterize the inflammatory infiltrate in ascending thoracic aortic aneurysm in patients with Marfan syndrome, familial thoracic aortic aneurysm, or nonfamilial thoracic aortic aneurysm...
  5. pmc Phospho-control of TGF-beta superfamily signaling
    Katharine H Wrighton
    Michael E DeBakey Department of Surgery, Department of Molecular and Cellular Biology and Dan L Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
    Cell Res 19:8-20. 2009
    ..This article illustrates the essential roles of reversible phosphorylation in controlling the strength and duration of TGF-beta signaling and the ensuing physiological responses...
  6. pmc Transforming Growth Factor {beta} Can Stimulate Smad1 Phosphorylation Independently of Bone Morphogenic Protein Receptors
    Katharine H Wrighton
    Michael E DeBakey Department of Surgery and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 284:9755-63. 2009
    ..Thus, TGFbeta-mediated Smad1 phosphorylation appears to occur via different receptor complexes in a cell type-specific manner...
  7. doi Serum myoglobin and renal morbidity and mortality following thoracic and thoraco-abdominal aortic repair: does rhabdomyolysis play a role?
    C C Miller
    Department of Cardiothoracic and Vascular Surgery, University of Texas Medical School at Houston, Memorial Hermann Heart and Vascular Institute, Houston, TX 77030, USA
    Eur J Vasc Endovasc Surg 37:388-94. 2009
    ..We studied postoperative myoglobinaemia and renal dysfunction following aortic surgery...
  8. pmc Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic disease
    Dong Chuan Guo
    The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
    Am J Hum Genet 84:617-27. 2009
    ....
  9. doi Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutations
    V Tran-Fadulu
    Department of Internal Medicine and Department of Neurosurgery, University of Texas Health Science Center at Houston, Texas, USA
    J Med Genet 46:607-13. 2009
    ..TGFBR2 mutations can also cause TAAD in the absence of features of LDS in large multigenerational families, yet only sporadic LDS cases or parent-child pairs with TGFBR1 mutations have been reported to date...
  10. doi Cerebrospinal fluid drainage during thoracic aortic repair: safety and current management
    Anthony L Estrera
    Department of Cardiothoracic and Vascular Surgery, University of Texas Medical School Houston, Houston, Texas, USA
    Ann Thorac Surg 88:9-15; discussion 15. 2009
    ..The benefit of cerebrospinal fluid (CSF) drainage during thoracic aortic repair has been established. Few studies, however, report management and safety of CSF drainage...
  11. doi Acute type A intramural hematoma: analysis of current management strategy
    Anthony Estrera
    Department of Cardiothoracic and Vascular Surgery, Memorial Hermann Heart and Vascular Institute, University of Texas at Houston Medical School, 77030, USA
    Circulation 120:S287-91. 2009
    ..Management of acute type A intramural hematoma (IMH) remains controversial, varying from immediate surgery to medical management only. Conversion to typical dissection remains a concern. We analyzed our experience managing acute type A IMH...
  12. pmc An adventitial IL-6/MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in mice
    Brian C Tieu
    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA
    J Clin Invest 119:3637-51. 2009
    ....
  13. pmc Expanding role of cyclin dependent kinases in cytokine inducible gene expression
    Allan R Brasier
    Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555 1060, USA
    Cell Cycle 7:2661-6. 2008
    ..The potential of inhibiting P-TEFb as an anti-inflammatory therapy in innate immunity and systemic inflammation will be discussed...
  14. doi Analysis of ascending and transverse aortic arch repair in octogenarians
    Pallav J Shah
    Cardiothoracic and Vascular Surgery, University of Texas Medical School at Houston, Houston, Texas, USA
    Ann Thorac Surg 86:774-9. 2008
    ..Increasing numbers of older patients are requiring complex thoracic aortic surgery. This retrospective study analyzed early and late outcomes after ascending and transverse arch surgery using hypothermic circulatory arrest (HCA)...
  15. ncbi Involvement of a novel Rac/RhoA guanosine triphosphatase-nuclear factor-kappaB inducing kinase signaling pathway mediating angiotensin II-induced RelA transactivation
    Sanjeev Choudhary
    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555 1060, USA
    Mol Endocrinol 21:2203-17. 2007
    ..RelA complex formation and inducible Ser(536) RelA phosphorylation...
  16. ncbi Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections
    Dong Chuan Guo
    Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA
    Nat Genet 39:1488-93. 2007
    ..These data, along with the previously reported MYH11 mutations causing familial TAAD, indicate the importance of SMC contraction in maintaining the structural integrity of the ascending aorta...
  17. pmc Saturation fluorescence labeling of proteins for proteomic analyses
    Elizabeth Pretzer
    Bayer HealthCare Pharmaceuticals, Berkeley, CA 94710, USA
    Anal Biochem 374:250-62. 2008
    ..We also showed that the dye exhibits little to no effect on the two-dimensional mobilities of labeled proteins derived from cells...
  18. doi Intraoperative skeletal muscle ischemia contributes to risk of renal dysfunction following thoracoabdominal aortic repair
    Charles C Miller
    Department of Cardiothoracic and Vascular Surgery, The University of Texas Medical School at Houston, Houston, TX 77030, USA
    Eur J Cardiothorac Surg 33:691-4. 2008
    ..Lacking complete historical laboratory data on myoglobinemia, we studied somatosensory evoked potential (SSEP) changes in the leg (a functional marker of leg ischemia), as a surrogate predictor of acute postoperative renal failure...
  19. doi Outcomes of delayed sternal closure after complex aortic surgery
    Anthony L Estrera
    Department of Cardiothoracic and Vascular Surgery, University of Texas Medical School and Memorial Hermann Hospital, Houston, TX 77030, United States
    Eur J Cardiothorac Surg 33:1039-42. 2008
    ..The objective of this study was to report our experience with open chest management and delayed sternal closure after complex proximal aortic surgery...
  20. doi Ascending and transverse aortic arch repair: the impact of glomerular filtration rate on mortality
    Anthony L Estrera
    Department of Cardiothoracic and Vascular Surgery, The University of Texas at Houston Medical School, Memorial Hermann Heart and Vascular Institute, Houston, TX 77030, USA
    Ann Surg 247:524-9. 2008
    ..We studied the impact of GFR on mortality following repair of ascending and arch aneurysms...
  21. pmc To (TGF)beta or not to (TGF)beta: fine-tuning of Smad signaling via post-translational modifications
    Katharine H Wrighton
    Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    Cell Signal 20:1579-91. 2008
    ..Recent progress, discussed herein, illustrates the critical roles of Smad post-translational modifications in the cellular outcome to TGF-beta signaling...
  22. pmc Biogenesis of short intronic repeat 27-nucleotide small RNA from endothelial nitric-oxide synthase gene
    Ming Xiang Zhang
    Adult Section of Cardiothoracic Surgery, Texas Heart Institute at St Luke s Episcopal Hospital, Division of Cardiothoracic Surgery, Michael E DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
    J Biol Chem 283:14685-93. 2008
    ..This novel molecular model may be responsible for quantitative differences between individuals carrying different numbers of the polymorphic repeats hence the cardiovascular risk...
  23. pmc Role of NonO-histone interaction in TNFalpha-suppressed prolyl-4-hydroxylase alpha1
    Cheng Zhang
    Division of Cardiovascular Surgery, the Texas Heart Institute at St Luke s Episcopal Hospital, Houston, Texas, USA
    Biochim Biophys Acta 1783:1517-28. 2008
    ..Defining this cytokine-mediated regulatory pathway may provide novel molecular targets for therapeutic intervention in preventing plaque rupture and acute coronary occlusion...
  24. doi Genetic basis of thoracic aortic aneurysms and dissections: focus on smooth muscle cell contractile dysfunction
    Dianna M Milewicz
    Department of Internal Medicine, University of Texas, Houston, Texas 77030, USA
    Annu Rev Genomics Hum Genet 9:283-302. 2008
    ....
  25. pmc Effect of 27nt small RNA on endothelial nitric-oxide synthase expression
    Ming Xiang Zhang
    Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012, China
    Mol Biol Cell 19:3997-4005. 2008
    ..Our study demonstrates that 27nt small RNA may suppress eNOS expression by altering histone acetylation and DNA methylation in regions adjacent to the 27nt repeat element and core promoter...
  26. pmc FBN1 mutations in patients with descending thoracic aortic dissections
    Ariel Brautbar
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
    Am J Med Genet A 152:413-6. 2010
    ....