Control of Cholesterol Metabolism and Plasma High - Density Lipoprotein Levels by microRNA - 144 Cristina

Foam cell formation because of excessive accumulation of cholesterol by macrophages is a pathological hallmark of atherosclerosis, the major cause of morbidity and mortality in Western societies. Macrophages cannot limit the uptake of cholesterol and, therefore, depend on cholesterol efflux pathways for preventing their transformation into foam cells. Several ABC transporters, including adenosine triphosphate–binding cassette transporter A1 (ABCA1) and adenosine triphosphate– binding cassette transporter G1 (ABCG1), facilitate the efflux of cholesterol from macrophages. ABCA1 and ABCG1 are thought to act in sequence to lipidate nascent and then mature high-density lipoprotein (HDL) to generate larger α-HDL particles destined for clearance by the liver. Mutations in the Abca1 gene cause Tangier disease, which is characterized by defects in cholesterol efflux and cholesterol ester accumulation in macrophages, and increase the risk of development of atherosclerosis. In the liver, ABCA1 also plays a critical role in the biogenesis of HDL and its deficiency leads to a dramatic reduction of plasma HDL levels.