Grant: Project Grant

We have developed an innovative cell viscoelasticity (i.e., elasticity and viscosity) imaging method to study macrophage biomechanics and its impact on phagocytosis of foreign bodies. We know from the Canadian HIV and Aging Cohort Study, leaded by our team, that premature atherosclerosis is enhanced in HIV individuals compared with age and sex-matched controls. One landmark of premature atherosclerosis development is the role played by blood monocytes-derived macrophages that accumulate within the artery wall to engulf oxidized low-density lipoproteins (LDL). Pro-inflammatory (M1 and M4 phenotype) and anti-inflammatory (M2 phenotype) macrophages were observed in specific spatial localizations of the atherosclerotic artery wall of people living with HIV (M1 and M4 macrophages are more abundant at sites of potential plaque rupture). We also have preliminary data showing the impact of senescence (i.e., premature aging) on macrophage stiffening. This study thus aims to provide an unexplored perspective on the role of macrophage viscoelasticity on its functionality in people living with HIV who develop premature aging and cardiovascular diseases. Our first objective will be to assess premature aging in HIV by determining the biological age of the immune system versus chronological age. The second objective will aim studying macrophage mechanics in chemically-induced senescence and for macrophages exposed to the HIV protein Tat. The last objective will be to study macrophage mechanics in people living with HIV with documented senescence and premature atherosclerosis. The uptake of modified LDL by monocytes-derived macrophages and their cholesterol efflux capacity will also be studied.