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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL083794-05
Application #
7864267
Study Section
Special Emphasis Panel (ZHL1-CSR-A (F1))
Program Officer
Mcdonald, Cheryl
Project Start
2006-05-05
Project End
2013-04-30
Budget Start
2010-05-01
Budget End
2013-04-30
Support Year
5
Fiscal Year
2010
Total Cost
$2,258,461
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800771594
City
Houston
State
TX
Country
United States
Zip Code
77225
Prakash, Siddharth K; Milewicz, Dianna M (2018) X Marks the Spot: The Profound Impact of Sex on Aortic Disease. Arterioscler Thromb Vasc Biol 38:9-11
Guo, Dong-Chuan; Hostetler, Ellen M; Fan, Yuxin et al. (2017) Heritable Thoracic Aortic Disease Genes in Sporadic Aortic Dissection. J Am Coll Cardiol 70:2728-2730
Ren, Pingping; Hughes, Michael; Krishnamoorthy, Swapna et al. (2017) Critical Role of ADAMTS-4 in the Development of Sporadic Aortic Aneurysm and Dissection in Mice. Sci Rep 7:12351
Wu, Darrell; Ren, Pingping; Zheng, Yanqiu et al. (2017) NLRP3 (Nucleotide Oligomerization Domain-Like Receptor Family, Pyrin Domain Containing 3)-Caspase-1 Inflammasome Degrades Contractile Proteins: Implications for Aortic Biomechanical Dysfunction and Aneurysm and Dissection Formation. Arterioscler Thromb Vasc Biol 37:694-706
Guo, Dong-Chuan; Grove, Megan L; Prakash, Siddharth K et al. (2016) Genetic Variants in LRP1 and ULK4 Are Associated with Acute Aortic Dissections. Am J Hum Genet 99:762-769
Romere, Chase; Duerrschmid, Clemens; Bournat, Juan et al. (2016) Asprosin, a Fasting-Induced Glucogenic Protein Hormone. Cell 165:566-79
van 't Hof, Femke N G; Ruigrok, Ynte M; Lee, Cue Hyunkyu et al. (2016) Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic Aneurysms. J Am Heart Assoc 5:
Prakash, Siddharth; Kuang, Shao-Qing; GenTAC Registry Investigators et al. (2016) Recurrent Rare Genomic Copy Number Variants and Bicuspid Aortic Valve Are Enriched in Early Onset Thoracic Aortic Aneurysms and Dissections. PLoS One 11:e0153543
Starosolski, Zbigniew; Villamizar, Carlos A; Rendon, David et al. (2015) Ultra High-Resolution In vivo Computed Tomography Imaging of Mouse Cerebrovasculature Using a Long Circulating Blood Pool Contrast Agent. Sci Rep 5:10178
Regalado, Ellen S; Guo, Dong-chuan; Prakash, Siddharth et al. (2015) Aortic Disease Presentation and Outcome Associated With ACTA2 Mutations. Circ Cardiovasc Genet 8:457-64

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