Atherosclerosis is one of the major causes of morbidity and mortality in the western world. The existing data of elevated expression levels of proteins like DNA damage and DNA repair enzymes in human atherosclerotic plaques are reviewed. From the literature, the effect of overexpression of different proteins using adenoviral vectors or the model of transgenic mice on the development of atherosclerosis will be discussed. Special focus is placed on the lysosomal acid lipase (LAL), because LAL connects extra-cellular with intra-cellular lipid metabolism and is the only hydrolase for cleavage of cholesteryl esters delivered to the lysosomes. Patients with a deficiency of LAL show an accumulation of lipids in the cells and develop pre-mature atherosclerosis. To answer the question of the influence of LAL in atherosclerosis if overexpressed, we show for the first time data of transgenic mice overexpressing LAL and the effect on the lipid level.