Evaluating new targets for treating cardiovascular disease and cardiotoxicity
Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality globally and there is a strong need for improved and more targeted treatments. The left ventricle of the heart is responsible for pumping blood around the body and CVD can result in left ventricular dysfunction (impaired contraction and/or relaxation) from a number of underlying causes. These include chronic high blood pressure, obesity and blood vessel damage that can lead to heart failure and poor prognosis for the patient. What is now also recognised is the contribution that certain drugs or devices can make to the overall CVD burden that leads to left ventricular dysfunction. Certain drugs and devices can have off-target effects - when the drug binds to targets other than those for which it was intended - that can lead to a condition termed cardiotoxicity (CTX). Anti-cancer drugs in particular can have both short-and long-term toxic off target effects on the heart and this can ultimately result in heart failure. The underlying reasons for this off-target CTX are not well understood.
As well as drug-induced CTX, patients with implants or devices have also been reported to present with varying degrees of off-target CTX as a result of the implant. In particular, patients with metal-on-metal (MoM) hip implants can suffer toxic off-target cardiovascular effects and this is due to cobalt ions being released over time from the MoM bearings and accumulating in the heart. Again, the mechanisms underlying cobalt-induced cardiotoxicity are not well understood.
The aims of this project, therefore, are to identify molecules or proteins within the heart that are directly associated with cardiac contractile dysfunction either as a result of underlying chronic hypertension or resulting from the toxic effects of drugs or biomaterials and to target the identified molecules or proteins with a view to reducing or reversing the cardiovascular damage.
In the short-term, the research information generated from this project will benefit a number of research groups from universities with whom we are currently collaborating and this will increase the capacity for research outputs in this field. The cardiovascular, cancer and orthopaedic research community will also benefit from our research outputs presented at national and international scientific meetings as well as networking events. In the medium term, the cardiology, oncology and orthopaedic clinical community will also benefit from research publications and ongoing collaborative projects. This work will inform potential treatments in clinical practice going forward. In the longer term, people with CVD, cancer or MoM hip implants will benefit from the research findings should the novel targets identified from this project be taken forward to clinical trials.