Karin Bornfeldt

Personal Information
Title Professor
Expertise Cardiovascular
Institution University of Washington
Data Summary
Grants/SubContracts 1
Progress Reports 1
Publications 2
Protocols 0
Committees 2


Diabetes and miRNA
Diabetes mellitus is associated with a number of devastating long-term complications, the most important in terms of increased mortality being macrovascular complications (atherosclerosis) leading to cardiovascular disease. In mouse models of diabetes-accelerated atherosclerosis, accumulation of macrophages in the blood vessel wall is due to a diabetes-induced inflammatory activation of these cells, and blocking this inflammatory activation completely prevents diabetes-accelerated atherosclerosis. We are therefore in the process of identifying intracellular mediators of this diabetes-induced macrophage inflammatory activation, with the hope of finding new drug targets to treat or prevent diabetes-accelerated atherosclerosis and perhaps other complications of diabetes that are dependent on macrophage activation. To this end, we have started to investigate the role of microRNAs in mediating diabetes-induced macrophage activation. Preliminary results demonstrate that diabetes causes marked suppression of microRNA-486-5p in macrophages. The best characterized and validated targets of microRNA-486 (miR-486) are Phosphatase and tensin homolog (PTEN; an inhibitor of PI3-kinase action) and Forkhead box protein O1 (FoxO1; a transcription factor downstream of PI3-kinase which promotes inflammation). The goal of this P&F project is to evaluate whether miR-486 is a mediator of diabetes-induced macrophage inflammatory activation. We propose to address two questions: 1). Is miR-486 suppressed by diabetes in monocytes and macrophages and is this associated with hyperglycemia and suppression of Ank1 expression?; and 2). Is downregulation of miR-486 in macrophages sufficient for inflammatory activation, mimicking the effect of diabetes? Our long-term goal is to identify new drug targets to deactivate monocytes and macrophages and prevent atherosclerosis and other diabetes complications.

Progress Reports

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ApplicationComplete DateReportOptions
Diabetes and miRNA (Bornfeldt, Karin)
10/30/2014View Progress Report Document

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