This Funding Opportunity Announcement (FOA) invites a single cooperative agreement application for a data coordinating center that first establishes a biorepository of human cardiovascular (CV) tissue and then serves as a coordinating center resource for discovery and mechanistic research to increase our knowledge of the CV complications of type 1 diabetes (T1D). Cardiovascular disease (CVD) is the leading cause of death and morbidity for individuals with T1D, but no T1D-specific therapy exists to prevent or treat this complication of diabetes because of challenges from inadequate preclinical models, decades-long disease progression and poorly defined differences in pathogenesis compared to type 2 diabetes (T2D). The FOA will support a two-phase research plan to encourage the use of human CV tissue to overcome these challenges. The goal of the first phase is to establish a biorepository through 1) the collection and storage of human cadaveric tissues from donors with T1D, T2D, and without diabetes; 2) the performance of quality control and basic histopathologic examination; and 3) the creation of a process for distribution of the biosamples and data to qualified investigators. The goal of the second phase is to serve as a coordinating center resource for investigators seeking to perform a multimodal analysis to deeply phenotype the anatomical, cellular, and molecular composition of the tissues and make the results available in a public data portal.
Cardiovascular complications are the leading cause of death for individuals with T1D and significantly shortens their lives. The T1D disease progression differs from that observed in T2D and in individuals without diabetes, with individuals with T1D, having a younger age of onset and a disproportionately greater effect on women. Treatment of standard risk factors such as hyperglycemia, hypertension, and hyperlipidemia, can ameliorate some, but not all the increased risk for CVD, so there remains residual risk after control of traditional risk factors. The pathophysiology of atherosclerosis, cardiomyopathy, and cardiac autonomic neuropathy in T1D is poorly understood and no therapies are approved to prevent or treat these common and deadly complications of T1D. Challenges to research on CVD in T1D are its silent development over decades of metabolic dysregulation and the lack of preclinical models that replicate the human disease. The goal of this FOA is to establish a biorepository and DCC for human CV tissue to advance and support discovery and mechanistic research that increase our understanding of CVD in T1D and lead to biomarkers for early detection and treatments specific for T1D.
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