Project
Active microvascular regression drives diastolic dysfunction leading to heart failure
Heart disease is the most important cause of mortality in westernized nations, with heart failure, which is when the heart cannot pump sufficient blood, being the most prominent cause of hospitalizations in Europe. More than half of the heart failure patients have heart failure with preserved ejection fraction (HFpEF). HFpEF occurs in patients that present with additional disorders such as diabetes and hypertension. There is currently no successful treatment for HFpEF. There is increasing evidence that the blood vessels that feed the heart tissue are dysfunctional during HFpEF and we have preliminary results showing that a reduction in blood vessel density is present in HFpEF. We also have gene analysis data showing that a gene, called Pitx2, is downregulated. This is important because in other model, Pitx2 downregulation drives vessels to regress. We will therefore investigate Pitx2 regulation in various models of heart failure, including biopsie samples from people who suffer from heart failure. This research represents a new perspective on HFpEF, focusing on blood vessel dysfunction rather than heart muscle cell dysfunction, as well as investigating why reduced blood vessel density occurs.