The Target of Regulating The ATP-binding Cassette A1 Protein (ABCA1): Promoting ABCA1-Mediated Cholesterol Efflux in Different Cells

Abstract

The ATP-binding cassette A1 (ABCA1) transporter plays a major role in the efflux of lipids by mediating the cellular transport of phospholipids and cholesterol to lipid-poor/lipid-free apolipoprotein A-I (apoA-I) particles and thereby exerting important anti-atherogenic effects. Although the mechanism whereby ABCA1 mediates cholesterol efflux is not completely understood, numerous studies have shown that, in addition to apoA-I, the expression level of the total or cell surface ABCA1 protein is a determining factor for the activity of ABCA1-mediated cholesterol efflux, and defects in ABCA1-mediated cholesterol efflux lead to various pathological conditions in different cells, including cardiovascular and metabolic disorders. It has been widely demonstrated that a growing list of natural and synthetic substances and metabolic regulators that modulate the expression of ABCA1 not only act directly on the ABCA1 gene promoter, but also occurs at the post-transcriptional level via micro-RNAs and post-translationally through the stabilization or localization of the protein. The complex regulatory network of ABCA1 results in promoting or suppressing cholesterol efflux from cells, therefore we speculate that the ABCA1 transporter is emerging as a novel therapeutic target for cardiovascular and metabolic disorders. Thus, ABCA1 is a key modulator of cellular cholesterol efflux and contributes to functional disorders in different types of cells.

Allicin induces the upregulation of ABCA1 expression via PPARγ/LXRα signaling in THP-1 macrophage-derived foam cells

“…The expression of the ABCA1 gene in macrophages is transcriptionally regulated by ligand-dependent nuclear receptors (8). Peroxisome proliferator-activated receptor γ (PPARγ) (a member of the nuclear receptor superfamily) enhances cholesterol efflux by inducing the transcription of the liver X receptor α (LXRα) gene and ABCA1 (9).…”

Dissecting Polygenic Etiology of Ischemic Stroke in the Era of Precision Medicine

“…The enriched pathways, such as “protein-lipid complex assembly” and “macrophage-derived foam cell differentiation”, confirm the pathology of atherosclerosis in the pathogenesis of IS and its subtypes. In addition, the phenotypic variation can be explained more by these relatively rare variants from genes (i.e., ABCA1, PPARG, PRKCH , and APOB ), which were actively engaged in the process of atherosclerosis and became a drug target for stroke [ 99 , 100 , 101 ]. As one of several low-frequency variants associated with IS in APOB , rs1800480 is an eQTL for LDL cholesterol levels with the same direction for higher LDL levels ( p = 1.6 × 10 −127 ) [ 102 ].…”

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“…Kolesterol yang telah disintesis akan berikatan dengan LDL reseptor kemudian ditranspor menuju sel hepar, yang kemudian digunakan untuk sintesis asam empedu (Liscum, 2002). HDL memindahkan partikel lemak melalui reseptor HDL yaitu scavenger receptor BI (SR-BI), yang memperantarai penarikan kolesterol dari HDL (Huang, 2013). Peningkatan kolesterol pada sel terjadi karena penyerapan lipoprotein yang mengandung kolesterol oleh reseptor (Kathleen et al, 2006).…”