Research Topics
Genomes and Genes | SCCOR in Thoracic Aortic Aneurysms and DissectionsSummaryPrincipal 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
| Scientific Experts
|
Detail Information
Publications
Apolipoprotein-J prevention of fetal cardiac myoblast apoptosis induced by ethanolYangxin 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...
An FBN1 pseudoexon mutation in a patient with Marfan syndrome: confirmation of cryptic mutations leading to diseaseDong 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...- Ascending and transverse aortic arch repair: the impact of retrograde cerebral perfusionAnthony 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... - Characterization of the inflammatory cells in ascending thoracic aortic aneurysms in patients with Marfan syndrome, familial thoracic aortic aneurysms, and sporadic aneurysmsRumin 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... - Phospho-control of TGF-beta superfamily signalingKatharine 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... - Transforming Growth Factor {beta} Can Stimulate Smad1 Phosphorylation Independently of Bone Morphogenic Protein ReceptorsKatharine 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... - 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... - Mutations in smooth muscle alpha-actin (ACTA2) cause coronary artery disease, stroke, and Moyamoya disease, along with thoracic aortic diseaseDong Chuan Guo
The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
Am J Hum Genet 84:617-27. 2009.... - Analysis of multigenerational families with thoracic aortic aneurysms and dissections due to TGFBR1 or TGFBR2 mutationsV 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... - Cerebrospinal fluid drainage during thoracic aortic repair: safety and current managementAnthony 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... - Acute type A intramural hematoma: analysis of current management strategyAnthony 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... - An adventitial IL-6/MCP1 amplification loop accelerates macrophage-mediated vascular inflammation leading to aortic dissection in miceBrian C Tieu
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, USA
J Clin Invest 119:3637-51. 2009.... - Expanding role of cyclin dependent kinases in cytokine inducible gene expressionAllan 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... - Analysis of ascending and transverse aortic arch repair in octogenariansPallav 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)... 
Involvement of a novel Rac/RhoA guanosine triphosphatase-nuclear factor-kappaB inducing kinase signaling pathway mediating angiotensin II-induced RelA transactivationSanjeev 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...- Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissectionsDong 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... - Saturation fluorescence labeling of proteins for proteomic analysesElizabeth 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... - Intraoperative skeletal muscle ischemia contributes to risk of renal dysfunction following thoracoabdominal aortic repairCharles 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... - Outcomes of delayed sternal closure after complex aortic surgeryAnthony 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... - Ascending and transverse aortic arch repair: the impact of glomerular filtration rate on mortalityAnthony 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... - To (TGF)beta or not to (TGF)beta: fine-tuning of Smad signaling via post-translational modificationsKatharine 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... - Biogenesis of short intronic repeat 27-nucleotide small RNA from endothelial nitric-oxide synthase geneMing 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... - Role of NonO-histone interaction in TNFalpha-suppressed prolyl-4-hydroxylase alpha1Cheng 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... - Genetic basis of thoracic aortic aneurysms and dissections: focus on smooth muscle cell contractile dysfunctionDianna M Milewicz
Department of Internal Medicine, University of Texas, Houston, Texas 77030, USA
Annu Rev Genomics Hum Genet 9:283-302. 2008.... - Effect of 27nt small RNA on endothelial nitric-oxide synthase expressionMing 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... - FBN1 mutations in patients with descending thoracic aortic dissectionsAriel Brautbar
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
Am J Med Genet A 152:413-6. 2010....