Internalization of Modified Lipids by CD36 and SR-A Leads to Hepatic Inflammation and Lysosomal Cholesterol Storage in Kupffer CellsReportar como inadecuado




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Background and Aims

Non-alcoholic steatohepatitis NASH is characterized by steatosis and inflammation, which can further progress into fibrosis and cirrhosis. Recently, we demonstrated that combined deletion of the two main scavenger receptors, CD36 and macrophage scavenger receptor 1 MSR1, which are important for modified cholesterol-rich lipoprotein uptake, reduced NASH. The individual contributions of these receptors to NASH and the intracellular mechanisms by which they contribute to inflammation have not been established. We hypothesize that CD36 and MSR1 contribute independently to the onset of inflammation in NASH, by affecting intracellular cholesterol distribution inside Kupffer cells KCs.

Methods and Results

Ldlr−-− mice were transplanted with wild-type Wt, Cd36−-− or Msr1−-− bone marrow and fed a Western diet for 3months. Cd36−-−- and Msr1−-−- transplanted tp mice showed a similar reduction in hepatic inflammation compared to Wt-tp mice. While the total amount of cholesterol inside KCs was similar in all groups, KCs of Cd36−-−- and Msr1−-−-tp mice showed increased cytoplasmic cholesterol accumulation, while Wt-tp mice showed increased lysosomal cholesterol accumulation.

Conclusion

CD36 and MSR1 contribute similarly and independently to the progression of inflammation in NASH. One possible explanation for the inflammatory response related to expression of these receptors could be abnormal cholesterol trafficking in KCs. These data provide a new basis for prevention and treatment of NASH.



Autor: Veerle Bieghs, Fons Verheyen, Patrick J. van Gorp, Tim Hendrikx, Kristiaan Wouters, Dieter Lütjohann, Marion J. J. Gijbels, Mari

Fuente: http://plos.srce.hr/



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