Neuropeptide-Y pathophysiology in the development of heart failure

Acute myocardial infarction (AMI) and chronic systolic heart failure (CHF) result in high levels of cardiac sympathetic stimulation, which is a poor prognostic indicator.

Whilst beta-blockers improve mortality in these conditions by preventing the action of the neurotransmitter noradrenaline, a substantial residual risk still remains.

I have recently shown that the co-transmitter neuropeptide-Y (NPY) is also released during AMI, leading to larger infarcts and life-threatening arrhythmia.

Moreover, our preliminary data show that in patients with severe CHF, local cardiac NPY levels correlate with mortality.

In this Senior Fellowship, I will establish whether peripheral venous NPY levels provide a new mechanistic biomarker in AMI and CHF patients and whether the ability to increase NPY levels through exercise provides further prognostic information regarding cardiac function.

By investigating NPY expression in human and rat tissue from normal hearts and those with CHF, and manipulating NPY neurochemistry using state-of-the-art imaging techniques, I will establish NPYs role in the pathophysiology of CHF, and determine whether specific NPY receptor blockers can attenuate the development of heart failure in-vivo