1. Substance P as an anti-fibrotic in the diabetic heart
A loss of neuropeptide called substance P occurs in diabetes. We have determined that this loss of substance P together with high glucose levels predispose the heart to develop fibrosis and increase heart inflammation. With close collaboration at the Wake Forest University in the USA, we are examining the benefit of substance P replacement as a therapy for cardiac fibrosis in diabetes.
2. The neurokinin-1 receptor as a regulator of cardiac fibrosis
We have shown that the neurokinin-1 receptor in the heart is important in the development of fibrosis in the hypertensive heart by regulating a number of cellular mechanisms. We are now attempting to determine the significance of the neurokinin-1 receptor on specific cell types and their interactions with each other.
3. Catestatin as an anti-fibrotic in the diabetic heart
Catestatin is a peptide derived from the chromogranin A precursor molecule and is known to be protective in the heart. We have recently found for the first time that catestatin is decreased in the model of hypertension, and its restoration can prevent cardiac fibrosis. This project will attempt to determine the mechanisms by which catestatin acts directly on cardiac cells in opposing fibrosis development in the hypertensive heart.
4. The orphan nuclear receptor Nr4a1 in cardiac fibrosis
We have identified that deletion of Nr4a1 prevents cardiac fibrosis and improves heart functions by regulating inflammation and communication between cardiac cell types. In this project, we will unravel the mechanisms by which Nr4a1 regulates inflammation and cardiac fibrosis.