The Role of the ATP-Binding Cassette A1 (ABCA1) in Human Disease

Abstract

Cholesterol homeostasis is essential in normal physiology of all cells. One of several proteins involved in cholesterol homeostasis is the ATP-binding cassette transporter A1 (ABCA1), a transmembrane protein widely expressed in many tissues. One of its main functions is the efflux of intracellular free cholesterol and phospholipids across the plasma membrane to combine with apolipoproteins, mainly apolipoprotein A-I (Apo A-I), forming nascent high-density lipoprotein-cholesterol (HDL-C) particles, the first step of reverse cholesterol transport (RCT). In addition, ABCA1 regulates cholesterol and phospholipid content in the plasma membrane affecting lipid rafts, microparticle (MP) formation and cell signaling. Thus, it is not surprising that impaired ABCA1 function and altered cholesterol homeostasis may affect many different organs and is involved in the pathophysiology of a broad array of diseases. This review describes evidence obtained from animal models, human studies and genetic variation explaining how ABCA1 is involved in dyslipidemia, coronary heart disease (CHD), type 2 diabetes (T2D), thrombosis, neurological disorders, age-related macular degeneration (AMD), glaucoma, viral infections and in cancer progression.

Role of ABCA7 in Human Health and in Alzheimer’s Disease

“…As indicated above, ABCA7 shares high amino sequence homology with other ABC transporters mediating lipid release from cell membranes, and in particular with ABCA1. This latter is the most studied ABC transporter in this cellular process and its role in cholesterol efflux to high-density lipoproteins (HDL) is very well characterized [ 29 , 30 , 31 ]. Mutations in the ABCA1 gene cause an inherited disease named Tangier disease in which the cholesterol transfer from cells to HDL is decreased, leading to lower ApoA-I synthesis as well as low levels of plasmatic HDL [ 32 ].…”

Expression of miRNAs Targeting ATP Binding Cassette Transporter 1 (ABCA1) among Patients with Significant Carotid Artery Stenosis

“…One of several proteins related to cholesterol homeostasis is ATP Binding Cassette Transporter 1 (ABCA1), a transmembrane protein extensively expressed in many tissues [25]. ABCA1 functions in the first and crucial step of HDL-C formation [26]. Considering that low HDL-C levels are an independent risk factor for coronary heart disease (CHD), genetic variants that are known to increase HDL-C levels would be expected to decrease CHD risk, whereas variants associated with lower HDL-C levels would increase CHD risk [27].…”

Bioinformatic Analysis of ABCA1 Gene Expression in Smoking and Chronic Obstructive Pulmonary Disease

“…In this regard, the role of ABCA1 is well known in the pathogenesis of atherosclerosis [ 47 ]. However, taking into account the high levels of ABCA1 expression in lung tissues, it becomes obvious that the function of the transporter is much more extensive than it was thought previously [ 48 , 49 , 50 ]. The significance of Abca1 for lung function is well demonstrated by experimental data with gene knockout in mice that develop pronounced morphological changes in the lungs that increase with age and are characterized by the accumulation of foamy macrophages, destruction of alveolar septa, and epithelization of the alveoli due to severe hypertrophy and hyperplasia of type II pneumocytes [ 51 ].…”