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CORONARY MICROVASCULAR SIGNALLING AS A CENTRAL DETERMINANT OF ADVERSE TISSUE REMODELLING AND DYSFUNCTION IN THE DIABETIC HEART

School of Medicine, Dentistry and Biomedical Sciences | PHD
Funding
Unfunded
Reference Number
SMED-2201-1072
Application Deadline
None specified
Start Date
None specified

Overview

The coronary microcirculation is recognised as playing an increasingly important role in determining development and progression of heart failure. This project will investigate its specific role in the diabetic heart, which is associated with microvascular disease, with the aim of identifying key underlying pathways for therapeutic targeting.

The diabetic heart is characterised by impaired coronary microvascular function leading to diastolic dysfunction, fibrosis, inflammation and cardiomyocyte remodelling, underlying elevated risk of heart failure. This often develops early but remains undiagnosed until patients become symptomatic so it is critical that underlying mechanisms are defined to inform specific diagnostic and therapeutic approaches. Our previous work indicates that altered endothelial cell biology in the diabetic heart is responsible for impaired vascular function and adverse tissue remodelling through modulation of key pathways such as reactive oxygen species and inflammatory signalling; however, precise mechanisms remain unknown. The specific objectives of this project are to (1) characterise cardiac remodelling and the contribution of coronary microvascular dysfunction in an experimental model of diet-induced diabetes, (2) study how diabetes influences communication between coronary endothelial cells and cardiac fibroblasts and cardiomyocytes, (3) identify candidate mediators which may be targeted to reduce adverse cardiac remodelling and dysfunction. The results of this study will provide detailed mechanistic insight in to precisely how the coronary microvasculature may direct detrimental remodelling of the diabetic heart. Such information is critical to inform development of novel clinical management strategies for diabetic heart failure for which there are currently no specific treatments available.

Project Summary
Supervisor

Professor David Grieve

Research Profile


Mode of Study

Full-time: 3 Years


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