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.
Highlights
Key functions, such as nutrient intake, sequestration of metabolic end products at the most primary level and the exchange of compounds between cellular organelles or even tissues in more advanced life forms, often take place against concentration gradients across cellular membranes
ABC transporters have been extensively investigated in diseases, such as cancer and cancer multidrug resistance, their importance in the pathogenesis of cardiovascular diseases (CVD) is just beginning to be elucidated
ABCA1 has been identified as an ABC transporter with a crucial role in high density lipoprotein (HDL)
Summary
Key functions, such as nutrient intake, sequestration of metabolic end products at the most primary level and the exchange of compounds between cellular organelles or even tissues in more advanced life forms, often take place against concentration gradients across cellular membranes. It is not surprising that in simple life forms like bacteria, almost ten percent of the entire genome is dedicated to proteins that are involved in transport processes in the form of membrane-bound or soluble proteins [1] Such transport processes against chemical gradients always require the use of free energy either by simultaneous use of an opposing electrochemical potential difference (secondary active transport) or a coupled enzymatic reaction exploiting the chemical energy of Adenosine triphosphate (ATP) hydrolysis (primary active transport). These ATP-driven transport proteins are called ATPases and compose a large superfamily including F-, A- and V-ATPases, P-type ATPases and ABC (ATP-binding cassette) transporters. ABC transporters are most abundantly expressed in organs with high metabolic rates and in endothelial tissues isolating certain organs from the rest of the body like the blood-brain barrier, blood-testis barrier and others
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