Coronary heart disease (CHD) is the UK's single biggest killer, leading to the death of nearly one in six men and one in ten women in the country. Approximately 2.3 million people in the UK are living with CHD. In 2009, the healthcare costs of this (medications, accident & emergency, primary/outpatient/inpatient care) amounted to nearly £2 billion, whilst informal care costs and productivity losses due to mortality and morbidity amounted to an additional £5 billion. The incidence of CHD correlates strongly with deprivation - mortality rates are almost twice as high in deprived areas compared with affluent areas. CHD occurs when the blood vessels of the heart (coronary arteries) become narrowed by fatty material (atheroma), reducing blood flow to the heart muscle. If the atheroma breaks off it can lead to the formation of a blood clot that could potentially block the coronary artery, cutting off the oxygen-rich blood supply to a part of the heart muscle and risking irreversible damage. The death of this part of the heart muscle is called a heart attack, also known as myocardial infarction (MI). Whilst the heart muscle that dies forms a scar, the surviving heart muscle around the scar undergoes numerous maladaptive changes that can dictate the outcome for the patient. Collectively, these changes are called pathological cardiac remodelling and can lead to a dilated heart that is unable to pump efficiently. A significant proportion of post-MI patients undergo progressive worsening of pathological cardiac remodelling and develop heart failure (HF), meaning that the heart can no longer pump enough blood to meet the needs of the body. Although improving, population morbidity and mortality remain high and new treatments are urgently required for patients with MI and HF. Runx1 is a protein that regulates the activity and expression of a number of other proteins important for the normal functioning of the body. Recently it has been discovered in patients with MI that increased levels of Runx1 are produced in the surviving heart muscle around the scar. Until now the function of Runx1 in the heart remained unknown. We have induced MI in a genetically modified mouse with selective reduction of Runx1 in the heart muscle cells (cardiomyocytes). Our experiments demonstrate compelling evidence that Runx1 is linked to how well the heart is able to pump post-MI. This proposal aims to uncover the mechanisms involved in this important link and in doing so drive forward future studies to determine the therapeutic potential of this novel target.