Mice expressing the human CYP7A1 gene in the mouse CYP7A1 knock-out background lack induction of CYP7A1 expression by cholesterol feeding and have increased hypercholesterolemia when fed a high fat diet.
Appraisal of the liver revealed an up-regulation of mRNA expressions of the small heterodimer partner (Shp) and attenuation of Cyp7a1, which contributed to hypercholesterolemia in vitamin D-deficiency.
EP4 deficiency negatively regulate bile acid synthesis through repression of phosphorylated extracellular signal-regulated kinase 1/2 (ERK)-mediated cholesterol 7α-hydroxylase (CYP7A1) expression and that the hypercholesterolemia in EP4 knockout mice is due to a defect in cholesterol conversion into bile acids.
The findings of the present study provide a positive role of ML on cholesterol clearance via promoting cholesterol and TBA execration via FXR- and CYP7A1-mediated pathways; RCT regulation may be a potential mechanism of ML on anti-hypercholesterolemia.
Collectively, these results indicate that atRA activates JNK and ERK pathways and the downstream target AP-1 represses HNF4α transactivation of the CYP7A1 promoter, potentially responsible for hypercholesterolemia.
The ACAT-2 and CYP7A1 mRNA expression were significantly decreased in HC diet supplemented with STG, while the mRNA levels of LDLR were markedly increased.
In addition, manipulating BA homeostasis by modulating cholesterol 7α-hydroxylase (CYP7A1) may affect the metabolic processing of cholesterol, exerting therapeutic effects on hypercholesterolemia and cardiovascular diseases.
Moreover, BS were capable of down-regulating CYP7A1 expression in MTs and elicited abnormal lipid production (accumulation) concordant with clinical cases where chronic cholestasis results in hypercholesterolemia.
The CYP7A1 gene polymorphism rs3824260 is related to inappropriate response of simvastatin treatment for hypercholesterolemia patients in Chinese Han population.