Hepatic expression of cholesterol regulating genes favour increased circulating low-density lipoprotein in HIV infected patients with gallstone disease: a preliminary study

Abstract

Background HIV endemic populations are displaying higher incidence of metabolic disorders. HIV and the standard treatment are both associated with altered lipid and cholesterol metabolism, however gallstone disease (a cholesterol related disorder) in Sub-Saharan African populations is rarely investigated. Methods This study sought to evaluate hepatic expression of key genes in cholesterol metabolism (LDLr, HMGCR, ABCA1) and transcriptional regulators of these genes (microRNA-148a, SREBP2) in HIV positive patients on antiretroviral therapy presenting with gallstones. Liver biopsies from HIV positive patients (cases: n = 5) and HIV negative patients (controls: n = 5) were analysed for miR-148a and mRNA expression using quantitative PCR. Results Circulating total cholesterol was elevated in the HIV positive group with significantly elevated LDL-c levels(3.16 ± 0.64 mmol/L) relative to uninfected controls (2.10 ± 0.74 mmol/L; p = 0.04). A scavenging receptor for LDL-c, LDLr was significantly decreased (0.18-fold) in this group, possibly contributing to higher LDL-c levels. Transcriptional regulator of LDLr, SREBP2 was also significantly lower (0.13-fold) in HIV positive patients. Regulatory microRNA, miR-148a-3p, was reduced in HIV positive patients (0.39-fold) with a concomitant increase in target ABCA1 (1.5-fold), which regulates cholesterol efflux. Conclusions Collectively these results show that HIV patients on antiretroviral therapy display altered hepatic regulation of cholesterol metabolizing genes, reducing cholesterol scavenging, and increasing cholesterol efflux.

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“… [ 37 ] HIV LDLR levels in mononuclear cells of the liver and blood are down-regulated in HIV-positive patients with lipodystrophy, independent of PI-ART, compared to HIV-negative controls and positive patients without lipodystrophy. [ 38 , 39 ] Dengue virus For DENV to proliferate and be introduced, cholesterol is essential. Furthermore, it was shown that soon after infection, there was an increase in lipid raft formation and total cholesterol levels.…”

Human Hepatocyte Nuclear Factors (HNF1 and LXRb) Regulate CYP7A1 in HIV-Infected Black South African Women with Gallstone Disease: A Preliminary Study

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Antiretroviral Therapy-Induced Dysregulation of Gene Expression and Lipid Metabolism in HIV+ Patients: Beneficial Role of Antioxidant Phytochemicals

“…The HIV-positive group had higher total cholesterol with significantly elevated LDL-C levels than uninfected controls, while the scavenging LDLR for LDL-C was significantly decreased in the HIV group. The transcriptional regulator of LDLR, SREBP2, was decreased in HIV-positive patients; besides this, the regulatory miR-148a-3p was reduced with a concomitant increase in target ABCA1, regulating cholesterol efflux [ 112 ].…”

“…ROS production is mediated by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) family complex as NOX1, NOX2, NOX4, and NOX5 [ 5 , 124 ]. NOX members are found in muscle tissue and represent the primary sources of ROS; its activity has been investigated in conditions such as hypertension, hypercholesterolemia, and endothelial dysfunction [ 110 , 111 , 112 , 125 , 126 , 127 ]. Another enzyme that generates ROS is xanthine oxidoreductase, principally found in the liver and gut, although distributed in smaller proportions in the lungs, kidneys, heart, and brain plasma.…”