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Lysosomal cholesterol accumulation: driver on the road to inflammation during atherosclerosis and non‐alcoholic steatohepatitis
Author(s) -
Hendrikx T.,
Walenbergh S. M. A.,
Hofker M. H.,
ShiriSverdlov R.
Publication year - 2014
Publication title -
obesity reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.845
H-Index - 162
eISSN - 1467-789X
pISSN - 1467-7881
DOI - 10.1111/obr.12159
Subject(s) - steatohepatitis , inflammation , cholesterol , disease , medicine , fatty liver , biology , endocrinology , immunology
Summary 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.