Lysosomal cholesterol accumulation: driver on the road to inflammation during atherosclerosis and non-alcoholic steatohepatitis

T. Hendrikx, S. Walenbergh, M.H. Hofker, R. Shiri-Sverdlov*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    Many studies show an association between the accumulation of cholesterol inside lysosomes and the progression towards inflammatory disease states that are closely related to obesity. While in the past, the knowledge regarding lysosomal cholesterol accumulation was limited to its association with plaque severity during atherosclerosis, recently, a growing body of evidence indicates a causal link between lysosomal cholesterol accumulation and inflammation. These findings make lysosomal cholesterol accumulation an important target for intervention in metabolic diseases that are characterized by the presence of an inflammatory response. In this review, we aim to show the importance of cholesterol trapping inside lysosomes to the development of inflammation by focusing upon cardiovascular disease and non-alcoholic steatohepatitis (NASH) in particular. We summarize current data supporting the hypothesis that lysosomal cholesterol accumulation plays a key role in the development of inflammation during atherosclerosis and NASH. In addition, potential mechanisms by which disturbed lysosomal function can trigger the inflammatory response, the challenges in improving cholesterol trafficking in macrophages and recent successful research directions will be discussed.
    Original languageEnglish
    Pages (from-to)424-433
    Number of pages10
    JournalObesity Reviews
    Volume15
    Issue number5
    DOIs
    Publication statusPublished - May 2014

    Keywords

    • obesity
    • Cholesterol
    • lysosomes
    • inflammation
    • LOW-DENSITY-LIPOPROTEIN
    • WHITE CARNEAU PIGEONS
    • MACROPHAGE FOAM CELLS
    • E-DEFICIENT MICE
    • OXIDIZED LDL
    • METABOLIC SYNDROME
    • STORAGE DISORDERS
    • REDUCES ATHEROSCLEROSIS
    • CYCLODEXTRIN OVERCOMES
    • HEPATIC LIPOTOXICITY

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