Plasma cholesteryl ester transfer protein is predominantly derived from Kupffer cells

Autor: Yanan Wang, Ko Willems van Dijk, Biljana Atanasovska, Patrick C.N. Rensen, Siroon Bekkering, Nathanja Tjeerdema, Jimmy F.P. Berbée, Marten H. Hofker, Sander S. Rensen, Niels P. Riksen, Jan Greve, Menno Hoekstra, Ronit Shiri-Sverdlov, Jingyuan Fu, Onno C. Meijer, Louis M. Havekes, Wim A. Buurman, Sam van der Tuin, Andrea D. van Dam, Tim Hendrikx, Johannes W. A. Smit
Přispěvatelé: RS: CARIM - R2 - Cardiac function and failure, RS: NUTRIM - R2 - Gut-liver homeostasis, Surgery, Moleculaire Genetica, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Center for Liver, Digestive and Metabolic Diseases (CLDM), Vascular Ageing Programme (VAP)
Rok vydání: 2015
Předmět:
Adult
Male
medicine.medical_specialty
Kupffer Cells
Adipose tissue
WEIGHT-LOSS
Mice
Transgenic
Transgenic
Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18]
chemistry.chemical_compound
Mice
High-density lipoprotein
HOST-DEFENSE
Internal medicine
Gene expression
Cholesterylester transfer protein
CETP TRANSGENIC MICE
medicine
Animals
Humans
FATTY LIVER-DISEASE
GENE-EXPRESSION
Aged
Messenger RNA
Fenofibrate
Hepatology
biology
NONALCOHOLIC STEATOHEPATITIS
INCREASES HDL
Vascular damage Radboud Institute for Molecular Life Sciences [Radboudumc 16]
Middle Aged
eye diseases
Cholesterol Ester Transfer Proteins
carbohydrates (lipids)
Endocrinology
ADIPOSE-TISSUE
chemistry
biology.protein
Female
lipids (amino acids
peptides
and proteins)
MESSENGER-RNA
HIGH-DENSITY-LIPOPROTEIN
Niacin
Lipoprotein
medicine.drug
Zdroj: Hepatology, 62, 1710-22
Hepatology, 62(6), 1710-1722
Hepatology, 62(6), 1710-1722. Wiley
Hepatology, 62, 6, pp. 1710-22
ISSN: 0270-9139
Popis: Contains fulltext : 152584.pdf (Publisher’s version ) (Closed access) The role of Kupffer cells (KCs) in the pathophysiology of the liver has been firmly established. Nevertheless, KCs have been underexplored as a target for diagnosis and treatment of liver diseases owing to the lack of noninvasive diagnostic tests. We addressed the hypothesis that cholesteryl ester transfer protein (CETP) is mainly derived from KCs and may predict KC content. Microarray analysis of liver and adipose tissue biopsies, obtained from 93 obese subjects who underwent elective bariatric surgery, showed that expression of CETP is markedly higher in liver than adipose tissue. Hepatic expression of CETP correlated strongly with that of KC markers, and CETP messenger RNA and protein colocalized specifically with KCs in human liver sections. Hepatic KC content as well as hepatic CETP expression correlated strongly with plasma CETP concentration. Mechanistic and intervention studies on the role of KCs in determining the plasma CETP concentration were performed in a transgenic (Tg) mouse model expressing human CETP. Selective elimination of KCs from the liver in CETP Tg mice virtually abolished hepatic CETP expression and largely reduced plasma CETP concentration, consequently improving the lipoprotein profile. Conversely, augmentation of KCs after Bacille-Calemette-Guerin vaccination largely increased hepatic CETP expression and plasma CETP. Also, lipid-lowering drugs fenofibrate and niacin reduced liver KC content, accompanied by reduced plasma CETP concentration. CONCLUSIONS: Plasma CETP is predominantly derived from KCs, and plasma CETP level predicts hepatic KC content in humans.(Hepatology 2015;62:1710-1722).
Databáze: OpenAIRE
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