Grants and Contracts Details
Description
Thoracic aortic aneurysm and dissection (TAAD) has high risk for fatal aortic rupture. The
pathogenesis of TAAD is complex, spanning a spectrum of known genetic and unknown spontaneous
etiologies. Mechanisms of TAAD have not been defined, which impede the development of effective medical
treatment. Conflicting interpretations of animal and human study findings also result in challenges to fully
understand the development and progression of this disease. Many mouse models are available, each
representing some, but not all aspects of the TAAD pathogenesis and mechanisms of the human disease. This
proposed R35 Research Program will primarily focus on understanding the complex pathophysiology and
mechanisms of TAAD using multiple mouse models with manipulations of a spectrum of molecules. The
potential causal findings in mouse models will be validated in human TAAD samples from Dr. LeMaire at the
Baylor College of Medicine. Dr. LeMaire has established a Thoracic Aortic Disease Tissue Bank housing
samples and corresponding phenotypic data from over 4,000 patients with TAAD and has served as a core for
the NHLBI-supported Specialized Center of Clinical Oriented Research (SCCOR) in TAAD. Three major
projects are proposed in this program. Project 1 aims to define the renin-angiotensin system-mediated
mechanisms and therapeutic potential for TAAD; Project 2 will determine whether smooth muscle cell
heterogeneity is a basis for regional and transmural location of pathology in TAAD; Project 3 will explore how
the extracellular matrix and crosstalk between smooth muscle cells and fibroblasts contribute to TAAD
development. We have robust tools including a spectrum of reagents, multiple classic and new mouse models,
ultrasonography, MRI, and state-of-the-art intravital microscopy, proteomics, and single cell RNA sequencing
techniques. In addition to aortic aneurysms, the PI has more than 30-year expertise in the fields of lipoprotein
metabolism, inflammation, and atherosclerosis research. TAAD is not a sole aortic disease, but is associated
with a wide range of diseases or syndromes that may affect skin, lung, kidney, brain, bone, and other organs.
The proposed research program will benefit from the flexibility to pursue potential contributions of other tissues
and organs to TAAD, and vice versa the influences of TAAD on other tissues and organs.
Status | Finished |
---|---|
Effective start/end date | 6/1/21 → 5/31/23 |
Funding
- National Heart Lung and Blood Institute: $839,592.00
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