Grant: Project Grant

Statistics Canada has reported that only 23% of Canadians over the age of 60 have normal blood pressure. The response of the heart to increased blood pressure is to get bigger. The heart muscle also becomes stiffer, through a process known as fibrosis, which makes it more difficult for the heart to contract and relax. Although the enlargement of the heart can initially help in maintaining adequate blood flow to the body, excessive growth can lead to heart failure. However, fibrosis is essential for the heart to heal following myocardial infarction. Similar to a telephone network, information is transmitted into cells, including cells in the heart, by signalling networks. Information is also distributed within cells by signalling molecules, known as kinases, in a manner similar to a telephone operator directing a call to the intended person. When this information arrives, the cell responds. ERK3 and ERK4 are kinases in cells in the heart known as fibroblasts (ERK3) and myocytes (ERK4). Fibroblasts are involved in regulating how stiff the walls of the heart are by producing many structural proteins including collagens. Myocytes are muscle cells that contract with each heartbeat. There is no information available on the roles of ERK3 and ERK4 in the heart; our preliminary data shows that reduced ERK3 expression attenuated the increase in collagen mRNA in an experimental model of high blood pressure whereas ERK4-deficiency increased collagen mRNA. This project is to determine the effects of ERK3 or ERK4 deletion on cardiac remodelling in response to high blood pressure or following myocardial infarction in male and female mice. These studies should reveal if ERK3 and or ERK4 are useful targets for the development of cardioprotective drugs. In addition to protecting the heart, it is also possible that such drugs may result in the regression of heart disease.