ABCA1
The ABCA1 gene product, ATP-binding cassette transporter A1, facilitates the mobilization of cellular cholesterol to plasma lipoproteins.
An important determinant of the process of cholesterol efflux is the movement of cholesterol from intracellular stores to the plasma membrane, which may involve the membrane-transport apparatus.
Pathology
germline mutations of ABCA1 in:
- Tangier disease (a severe HDL deficiency syndrome characterized by accumulation of cholesterol in tissue macrophages and prevalent atherosclerosis) (MIM.205400)
- high density lipoprotein deficiency (MIM.604091)
- protection against coronary heart disease in familial hypercholesterolemia (FH) (MIM.143890)
NB: Susceptibility to atherosclerosis may in some cases be linked to variations in the gene ABCA1 found recently to be defective in patients with Tangier disease and familial high-density lipoprotein deficiency.
Physiopathology
Cholesterol is an essential component of eukaryotic membranes. To prevent the toxicity associated with cholesterol overload, cells transport excess cholesterol across the plasma membrane in part through the ABCA1 lipid transporter.
The discovery that mutations in ABCA1 are associated with high-density lipoprotein (HDL)-deficiency syndromes led to studies that show ABCA1, through its transport of cholesterol and phospholipid to apolipoprotein acceptors in the bloodstream, is crucial for the formation of HDL particles.
In the intestine, ABCA1 transports cholesterol from the epithelial cells to the bloodstream, contributing to approximately one-third of HDL production.
In the arterial wall, excess cholesterol in macrophages is associated with atherosclerosis; here, ABCA1 is anti-atherogenic because it enables macrophages to rid themselves of excess cholesterol.
References
Attie AD. ABCA1: at the nexus of cholesterol, HDL and atherosclerosis. Trends Biochem Sci. 2007 Feb 23; PMID: #17324574#
Oram JF. Molecular basis of cholesterol homeostasis: lessons from Tangier disease and ABCA1. Trends Mol Med. 2002 Apr;8(4):168-73. PMID: #11927274#