The interplay between lipid handling, inflammation and autophagy: Implications for cardiovascular disease and longevity

BackgroundAutophagy is a conserved self-protecting process involved in lipid handling and inflammation but the role in the pathogenesis of cardiovascular complications in type 2 diabetes (T2D) is largely unknown AimsExamine how autophagy pathways involved in lipid handling are affected by metformin treatment in relation to cardiovascular disease (CVD) and longevityCharacterize the role of autophagy markers in relation to plaque developmentResearch plan:Autophagy, lipid handling and inflammation in relation to atherogenesis are studied using a genetic approach; (i) macrophages from subjects carrying variants of perilipin 2 (PLIN2) that affects lipid handling are treated with metformin, followed by analysis of foam cell formation and cholesterol efflux (ii) atherosclerosis progression and plaque composition are studied in several cohorts and biobanks (iii) studies of Plin2-deficient miceAutophagy pathways during foam cell formation are studied using different inhibitors of autophagy processes followed by bioinformatic analyses in primary macrophages.

Links between autophagy markers and carotid plaque composition are studied in two plaque biobanks by molecular and cell biological analyses.

Mechanistic studies are performed in primary macrophages and in different atherogenic mice modelsSignificance:Better understanding of the interplay between lipid handling, inflammation and autophagy is likely to provide new therapeutic approaches to reduce CVD in patients with and without T2D