Grant: Travel Awards - Institute Community Support

Cardiovascular death is one of the leading causes of death in Canada. It is an economic burden to the health care system. Since the introduction of cholesterol lowering drugs, mainly statin, the cardiovascular death has been greatly reduced. In 21st century, scientists are in pursuit of a new therapy. High-density lipoprotein cholesterol (HDL-C) is also known as the good cholesterol; it is anti-inflammatory and athero-protective. In vivo data in mice have shown that HDL from healthy human subjects can promote carotid artery endothelial cells repair in mice (Besler et al., 2011). Low level of HDL is considered as a risk factor for cardiovascular events. However, little is understood in the field of HDL biogenesis, many HDL mimetic raising therapies failed in the past few years. Drugs designed to raise HDL increased HDL level up to 50%; however, no health benefits have been observed. HDL is a circulatory particle, and it has different sizes with different roles. For example small HDL (HDL3) is more protective against LDL oxidation compare to larger HDL (HDL2). It is possible that the mechanism of nascent HDL has not been fully understood, and the drugs designed to raise HDL-C caused off target effects. It is known that there are many difference HDL particles in circulation, and they do not react the same way in human body. This research project is highly translational. The goal is to elucidate the mechanism of HDL generation. Our data suggest that plasma membrane lipids have a role to play in HDL generation and cholesterol transfer. Human primary cells are used as our working model. We are answering this question using both biochemical techniques and bioinformatics methods. By studying HDL generation, it provides new ways to think about HDL-C raising therapy, and it can contribute to the elimination of those off target and non-specific effects.