Research

The overall research interests of the Hatter Cardiovascular Institute (HCI) include myocardial protection and the pathophysiology of ischaemia/reperfusion injury. More specifically we focus on developing ways to protect the diabetic and non-diabetic myocardium from the consequences of ischaemic and reperfusion-induced injury. This has involved an understanding of the pathophysiology of ischaemic heart disease at both the cellular, molecular and clinical levels. The HCI is noted for its translational approach to research, incorporating cellular-based models through to the clinical setting.

An important component of our research interests include the concept of “myocardial and remote preconditioning and post-conditioning”, potent endogenous adaptive mechanisms for protecting the heart against ischaemia-reperfusion injury. Concurrently, we are developing new pharmacological and therapeutic strategies to protect the myocardium from reperfusion-induced injury based upon our understanding of pro-survival signal transduction pathways and the contribution of mitochondria to cell survival that can be exploited to the benefit of the patient with ischaemic heart disease.

Complementing our cardioprotection programme are now three additional research arms: (1) neuroprotection specific to ischaemic stroke, (2) the cardio-renal syndrome, protecting the heart from the damage caused by chronic kidney disease and (3) cardio-oncology, investigating how best to reduce the damage to the heart following chemotherapy. 
 

Cardioprotection

The Hatter Cardiovascular Institute undertakes translational research focusing on the pathophysiology of Ischaemic Heart Disease in the young and aging myocardium in both the normal heart as well as in settings of co-morbidities such as diabetes and the metabolic syndrome. The research undertaken within the HCI explores the treatment strategies for protecting the heart at both a cellular & molecular level as well as in patients at risk of myocardial infarction.

This is undertaken in our purpose built and well-equipped laboratories through a wholly integrated approach employing a variety of experimental models. The research is directly translational, using the primary animal and human cardiomyocyte, the in vitro and in vivo perfused transgenic animal model and human muscle/artery through to clinical studies of patients with coronary heart disease undergoing CABG surgery and primary PCI. In all these settings, basic and clinical scientists focus on identifying the mechanism and signalling pathways associated with cellular injury and protection, with the ultimate aim of identifying new therapeutic targets and agents to protect the heart from acute myocardial infarction.

Over the past decades, through research funded by the British Heart Foundation (BHF), we have now developed a novel, drug called UCL-TRO-1938 that stimulates pro- survival pathways in the heart. We propose to use this drug as a tool to improve its potential effectiveness in humans. Through a further 5-year BHF Programme Grant, we will progress this research via a variety of laboratory experiments to confirm our hypothesis that the drug will be effective in the setting of relevant co- morbidities such as age and diabetes, which are common in heart attack patients.

Neuroprotection

The Hatter Cardiovascular Institute has initiated a Neuroprotection Group with the aim of using the knowledge we have in the cardiovascular ischaemia-reperfusion field to protect the brain from ischaemic stroke. This has been underpinned by a significant grant via the British Heart Foundation.

The management of stroke and acute myocardial infarction are similar and consist primarily of achieving rapid and complete reperfusion of the ischaemic tissue by endovascular procedures.

Working together, basic and clinical researchers seek to translate basic science findings into the design of novel appropriate adjunctive therapies which can protect from the reperfusion injury that occurs in the heart and brain.

The Cardio-renal syndrome

Patients with chronic kidney disease (CKD) have damaged kidneys which prevent them from eliminating toxic waste and bodily fluids. CKD not only affects the kidneys but also affects the function of other organs, especially the heart. Hence, patients with CKD have a higher risk of developing heart and circulatory problems such as heart attacks.
Through generous support of the British Heart Foundation and the Thompson Family Trust, we have developed a cardio-renal research programme to identify novel cardioprotective targets and also investigate innovative therapeutic options for the treatment of heart attack in the setting of CKD.

 

Cardioprotection following Cancer Therapy

Cardio-oncology is a rapidly emerging research area.  The Hatter Cardiovascular Institute has established a Cardio-Oncology Program which brings together Cardiologists, Oncologists and basic & clinical scientists from the HCI and the Macmillan Cancer Hospital at UCL/UCLH who all work together in promoting the cardiovascular health of UCLH cancer patients.

Our comprehensive cardio-oncology program provides care for patients who may have cardiac side-effects from traditional cancer therapies, such as anthracyclines and radiation, or novel targeted therapies.

This is underpinned by a comprehensive basic & clinical research group whose aim is to use the skills and knowledge obtained in the cardiovascular protection field, to protect the heart of patients on chemotherapy.