Grant: Project Grant

Cardiovascular diseases are a major health issue around the world and the leading cause of death in North America. Our research has uncovered a new protein, ACLY, that may be responsible for genetic and metabolic reprogramming linked to the development of diseases associated with thickening of blood vessel wall. We are now proposing a study to understand how ACLY contributes to the development of vascular diseases, and to demonstrate whether inhibition of ACLY can safely reverse these diseases. If successful, this research could have a rapid positive impact on the health of Canadian patients suffering from cardiovascular diseases, as ACLY inhibitors are already in existence and are non-toxic. Role of ACLY will be specifically explored in the process of neointimal hyperplasia. Neointimal hyperplasia is orchestrated by the interplay of metabolic and epigenetic signalling pathways, which are linked in a complex manner by ACLY and regulate gene expression. ACLY influence epigenetic pathways, such as acetylation, which in turn can alter the expression of genes involved in neointimal hyperplasia. Furthermore, epigenetic pathways can modulate the activity of metabolic enzymes, such as those involved in glycolysis and fatty acid oxidation, which further affects the expression of genes associated with neointimal hyperplasia. Therefore, both metabolic and epigenetic pathways must be considered when attempting to understand the mechanisms of neointimal hyperplasia.