Atherosclerosis is the leading cause of cardiovascular death globally and occurs when cholesterol builds up along the inner wall of blood vessels. While late-stage atherosclerosis is well understood, the underlying developmental stages prior to cholesterol elevation have not been explored. Mutations in the LDLR gene lead to a hereditary and accelerated form of atherosclerosis. In this study, we will focus on HSP70, a protein that responds to cellular stress and damage, during developmental atherosclerosis. Using an embryonic ldlr mutant zebrafish model, Hsp70 was found increased in cells that line blood vessels, which altered vascular and immune cell growth. We will use LDLR mutant endothelial cell and zebrafish models to determine the role of HSP70 in subcellular transport and early atherosclerosis progression. This work will be performed at the University of Helsinki, Biomedicum. Importantly, our findings will aid in understanding and treating the earliest stages of atherosclerosis.

2025

2029