Grant: CIHR Fellowship

Currently around 25% North Americans suffer from a condition known as metabolic syndrome. Metabolic syndrome is defined as a cluster of abnormalities including obesity, insulin resistance and increased blood pressure which together substantially increase risk of developing cardiovascular diseases, such as heart failure. Among patients with metabolic syndrome around 13.4% of them also have increased levels of iron. Several research studies have shown that increased iron levels can have a detrimental effect on the health of these individuals. While there have been studies investigating the role of increase iron in other tissues and conditions, we contend that iron is still an underappreciated factor in the development of heart failure in patients with metabolic syndrome. First, using isolated heart cells and establish cell lines, we will confirm our preliminary data that increased iron causes insulin resistance. Further, we will investigate and determine the role that autophagy and the NRLP3 inflammasome play in the development of insulin resistance when there is an increased iron present. Secondly, based on the results of the cell culture experiments, we will investigate these mechanisms in mouse models which lack either autophagy or the NLRP3 inflammasome to determine their effects on the heart. Taken together we aim to conduct a focused and in-depth analysis of mechanisms responsible for development of cardiovascular diseases under conditions on increased Iron. New knowledge from studies such as this are needed to pave the way for development of improved therapeutic strategies for treating patients with cardiovascular disease.