Increased hepatic ABCA1 transporter is associated with hypercholesterolemia in a cholestatic rat model and primary biliary cholangitis patients

• Published in: Medical molecular morphology Vol. 50; no. 4; pp. 227 - 237
• Main Authors: Takeyama, Yasuaki, Uehara, Yuko, Anan, Akira, Morihara, Daisuke, Yokoyama, Keiji, Takata, Kazuhide, Tanaka, Takashi, Irie, Makoto, Iwata, Kaoru, Shakado, Satoshi, Sohda, Tetsuro, Sakisaka, Shotaro
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.12.2017; Springer Nature B.V
• Subjects: ABCA1 protein; Anatomy; Animals; ATP Binding Cassette Transporter 1 - antagonists & inhibitors; ATP Binding Cassette Transporter 1 - genetics; ATP Binding Cassette Transporter 1 - metabolism; ATP-binding protein; Bile; Biological Transport; Cell Line, Tumor; Cholangitis; Cholestasis; Cholestasis, Intrahepatic - genetics; Cholestasis, Intrahepatic - metabolism; Cholestasis, Intrahepatic - pathology; Cholesterol; Cholesterol - metabolism; Disease Models, Animal; Gene expression; Gene Expression Regulation; Hepatocytes - metabolism; Hepatocytes - pathology; Humans; Hypercholesterolemia; Hypercholesterolemia - genetics; Hypercholesterolemia - metabolism; Hypercholesterolemia - pathology; Liver; Liver - metabolism; Liver - pathology; Liver Cirrhosis, Biliary - genetics; Liver Cirrhosis, Biliary - metabolism; Liver Cirrhosis, Biliary - pathology; Liver X receptors; Liver X Receptors - genetics; Liver X Receptors - metabolism; Male; Medicine; Medicine & Public Health; Molecular Medicine; mRNA; Original Paper; Pathology; Rats; Rats, Wistar; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Rodents; Signal Transduction; siRNA; ABCA1; PBC; Southwestern histochemistry; Hypercholesterolemia; Cholestasis
• ISSN: 1860-1480; 1860-1499
• DOI: 10.1007/s00795-017-0166-7

Hepatic ATP-binding cassette A1 (ABCA1) transporter is the modulator of intrahepatic cholesterol levels via the efflux of cholesterol into plasma. This study aimed to determine the expression of hepatic ABCA1 levels in a cholestatic rat model and patients with primary biliary cholangitis (PBC). A cholesterol efflux study was conducted with Abca1 knock down using siRNA in WIF9 cells. Cholesterol levels in the ABCA1 siRNA cells in the medium were significantly decreased compared with those in controls ( P  < 0.05). Hepatic ABCA1 mRNA levels were significantly higher in BDL rats than in control rats ( P  < 0.05). Furthermore, the protein expression level of hepatic ABCA1 was also significantly increased by 200% in BDL rats ( P  < 0.05). In PBC patients, expression of hepatic ABCA1 mRNA was 2.2-fold higher than that in controls ( P  < 0.05). The level of hepatic liver X receptor (LXR)β mRNA was correlated with ABCA1 mRNA levels in PBC patients. The expression of hepatic ABCA1 transporter was upregulated in both the cholestatic rat model and PBC patients. Upregulated hepatic ABCA1 may lead to efflux of cholesterol into plasma, thus explaining the mechanism of cholestasis leading to hypercholesterolemia.