Cardiovascular disease (CVD) is a leading cause of death world-wide, and certain populations who experience chronic inflammation, including aged individuals and people living with HIV (PLWH), have an increased risk of CVD. Most CVD starts with a thickening of the artery wall known as atherosclerosis.

We have developed a unique in vitro model of early atherosclerotic events that allows us to study the process of blood monocytes migrating into the blood vessel wall and forming fat-filled cells called “foam cells” which drive atherosclerosis. Using this assay, we have made the novel discovery that monocytes from aged individuals and PLWH have a greater propensity to develop into these atherosclerosis-promoting foam cells, and that this process is heightened by inflammation. What causes this is not known, but we are exploring the following:

• Investigating a novel species of “good cholesterol” found in PLWH which is dysfunctional and heightens foam cell formation.
• Isolating mRNA from monocytes from aged individuals and PLWH and using RNASeq to analyse the expression of genes involved in cholesterol synthesis, metabolism and transport.
• Assessing cholesterol uptake and efflux by monocytes using established assays.
• Exploring treatments and drugs which reverse or inhibit cholesterol accumulation and foam cell formation.

Timeline

2016 – 2019