Recent advances in the critical role of the sterol efflux transporters ABCG5/G8 in health and disease

Helen H. Wang, Min Liu, Piero Portincasa, David Q.H. Wang

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

Cardiovascular disease is characterized by lipid accumulation, inflammatory response, cell death, and fibrosis in the arterial wall and is the leading cause of morbidity and mortality worldwide. Cholesterol gallstone disease is caused by complex genetic and environmental factors and is one of the most prevalent and costly digestive diseases in the USA and Europe. Although sitosterolemia is a rare inherited lipid storage disease, its genetic studies led to identification of the sterol efflux transporters ABCG5/G8 that are located on chromosome 2p21 in humans and chromosome 17 in mice. Human and animal studies have clearly demonstrated that ABCG5/G8 play a critical role in regulating hepatic secretion and intestinal absorption of cholesterol and plant sterols. Sitosterolemia is caused by a mutation in either the ABCG5 or the ABCG8 gene alone, but not in both simultaneously. Polymorphisms in the ABCG5/G8 genes are associated with abnormal plasma cholesterol metabolism and may play a key role in the genetic determination of plasma cholesterol concentrations. Moreover, ABCG5/G8 is a new gallstone gene, LITH9. Gallstone-associated variants in ABCG5/G8 are involved in the pathogenesis of cholesterol gallstones in European, Asian, and South American populations. In this chapter, we summarize the latest advances in the critical role of the sterol efflux transporters ABCG5/G8 in regulating hepatic secretion of biliary cholesterol, intestinal absorption of cholesterol and plant sterols, the classical reverse cholesterol transport, and the newly established transintestinal cholesterol excretion, as well as in the pathogenesis and pathophysiology of ABCG5/G8-related metabolic diseases such as sitosterolemia, cardiovascular disease, and cholesterol gallstone disease.

Original languageEnglish (US)
Title of host publicationAdvances in Experimental Medicine and Biology
PublisherSpringer
Pages105-136
Number of pages32
DOIs
StatePublished - 2020

Publication series

NameAdvances in Experimental Medicine and Biology
Volume1276
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019

Keywords

  • Bile flow
  • Bile salts
  • Biliary lipid secretion
  • Cardiovascular disease
  • Cholesterol-lowering drugs
  • Coronary heart disease
  • Gallstones
  • Intestinal lipid absorption
  • Lith gene
  • Lithogenic bile
  • Reverse cholesterol transport
  • Statins
  • Stroke

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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