Grant: Project Grant

Heart failure (HF) is a cardiovascular (CV) condition caused by the inability of the cardiac muscle to provide enough blood flow and oxygen to muscles and organs. There are two types of HF, first, the classical form taking place mainly following a partial cardiac muscle death after a heart attack, reducing the capacity of the heart to pump blood, termed HF with reduced ejection fraction (HFrEF); second, there is a rapid rising form of HF, mainly caused by population aging, characterized by a stiff, yet almost normally contracting heart, and termed HF with preserved ejection fraction (HFpEF). HFpEF is characterized by chronic inflammation and mounting evidence suggest that neutrophils which are the most abundant circulating white blood cells might play a major role in the development of the pathology. Neutrophils have the capacity to release a meshwork of filaments termed NETs, which are linked to inflammatory proteins. The presence of those NETs in the circulation might lead to microvascular occlusion and exacerbate the progression of HFpEF. This is a novel observation from our group. Since all pharmacological approaches, have so far, not provided successful results to treat HFpEF adverse events, we are aiming to address the role of NETs in the progression of HFpEF both in animal models (mice) and HFpEF patients. In addition, we will be using an anti-inflammatory drug, colchicine which has a potent blocking effect on neutrophils. Consequently, we will be able to assess if colchicine can block the release of NETs by the neutrophils, and if it can contribute to stop or delay the progression of HFpEF disease both in mice and humans.