ABC Transport Proteins in Cardiovascular Disease—A Brief Summary

Abstract

Adenosine triphosphate (ATP)-binding cassette (ABC) transporters may play an important role in the pathogenesis of atherosclerotic vascular diseases due to their involvement in cholesterol homeostasis, blood pressure regulation, endothelial function, vascular inflammation, as well as platelet production and aggregation. In this regard, ABC transporters, such as ABCA1, ABCG5 and ABCG8, were initially found to be responsible for genetically-inherited syndromes like Tangier diseases and sitosterolemia. These findings led to the understanding of those transporter’s function in cellular cholesterol efflux and thereby also linked them to atherosclerosis and cardiovascular diseases (CVD). Subsequently, further ABC transporters, i.e., ABCG1, ABCG4, ABCB6, ABCC1, ABCC6 or ABCC9, have been shown to directly or indirectly affect cellular cholesterol efflux, the inflammatory response in macrophages, megakaryocyte proliferation and thrombus formation, as well as vascular function and blood pressure, and may thereby contribute to the pathogenesis of CVD and its complications. Furthermore, ABC transporters, such as ABCB1, ABCC2 or ABCG2, may affect the safety and efficacy of several drug classes currently in use for CVD treatment. This review will give a brief overview of ABC transporters involved in the process of atherogenesis and CVD pathology. It also aims to briefly summarize the role of ABC transporters in the pharmacokinetics and disposition of drugs frequently used to treat CVD and CVD-related complications.

Hereditary stomatocytosis: An underdiagnosed condition

“…Both genes ABCG5 and ABCG8 are located head to head on chromosome 2p21, and each gene encodes a “half‐ATP binding cassette transporter” that is nonfunctional in the monomeric state and that pump sterols out to intestinal lumen or into bile . However, assembly of an ABCG5/G8 heterodimer, driven by the adipocyte‐derived hormone leptin, leads to the formation of the fully‐functional transporter ABCG5/G8 . It has been demonstrated that ABCG5/G8 is exclusively expressed on the apical membranes of enterocytes and hepatocytes .…”

“…It has been demonstrated that ABCG5/G8 is exclusively expressed on the apical membranes of enterocytes and hepatocytes . The heterodimer is responsible for the efflux of cholesterol and plant sterols either by hepatocytes into the bile or through the enterocytes of the intestine back into the intestinal lumen for fecal disposal …”

Apigenin Retards Atherogenesis by Promoting ABCA1-Mediated Cholesterol Efflux and Suppressing Inflammation

“…ABCA1 can prevent foam cell formation by exporting excessive cholesterol from lipid-loaded macrophages and maintain cellular lipid and cholesterol homeostasis [33]. Firstly, we examined the effects of apigenin on macrophage ABCA1 expression and ABCA1-mediated cholesterol efflux.…”

Glucose and Lipid Transporters Roles in Type 2 Diabetes

“…GLUT2 movement to the apical membrane may be concerted with insulin signaling. Therefore, insulin resistance in T2DM would lead to increased and less regulated GLUT2 translocation to the apical membrane and glucose absorption, causing higher hyperglycemia in T2DM cases [13,18]. There exists a correlation between fructose consumption through food and T2DM occurrence, and fructose transporter GLUT5 may also play a role in the development of T2DM.…”