Next Article in Journal
Thromboembolic Complications of SARS-CoV-2 and Metabolic Derangements: Suggestions from Clinical Practice Evidence to Causative Agents
Previous Article in Journal
Identification of Circulating Diagnostic Biomarkers for Coronary Microvascular Disease in Postmenopausal Women Using Machine-Learning Techniques
Article

The Impact of Simvastatin on Lipidomic Markers of Cardiovascular Risk in Human Liver Cells Is Secondary to the Modulation of Intracellular Cholesterol

1
Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia
2
Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC 3004, Australia
3
Lipid Metabolism & Cardiometabolic Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia
4
Baker Department of Cardiometabolic Health, University of Melbourne, Parkville, VIC 3010, Australia
*
Authors to whom correspondence should be addressed.
Academic Editor: Manfredi Rizzo
Metabolites 2021, 11(6), 340; https://doi.org/10.3390/metabo11060340
Received: 27 April 2021 / Revised: 19 May 2021 / Accepted: 21 May 2021 / Published: 25 May 2021
(This article belongs to the Section Lipid Metabolism)
Statins are the first-line lipid-lowering therapy for reducing cardiovascular disease (CVD) risk. A plasma lipid ratio of two phospholipids, PI(36:2) and PC(18:0_20:4), was previously identified to explain 58% of the relative CVD risk reduction associated with pravastatin, independent of a change in low-density lipoprotein-cholesterol. This ratio may be a potential biomarker for the treatment effect of statins; however, the underlying mechanisms linking this ratio to CVD risk remain unclear. In this study, we investigated the effect of altered cholesterol conditions on the lipidome of cultured human liver cells (Hep3B). Hep3B cells were treated with simvastatin (5 μM), cyclodextrin (20 mg/mL) or cholesterol-loaded cyclodextrin (20 mg/mL) for 48 h and their lipidomes were examined. Induction of a low-cholesterol environment via simvastatin or cyclodextrin was associated with elevated levels of lipids containing arachidonic acid and decreases in phosphatidylinositol species and the PI(36:2)/PC(18:0_20:4) ratio. Conversely, increasing cholesterol levels via cholesterol-loaded cyclodextrin resulted in reciprocal regulation of these lipid parameters. Expression of genes involved in cholesterol and fatty acid synthesis supported the lipidomics data. These findings demonstrate that the PI(36:2)/PC(18:0_20:4) ratio responds to changes in intracellular cholesterol abundance per se, likely through a flux of the n-6 fatty acid pathway and altered phosphatidylinositol synthesis. These findings support this ratio as a potential marker for CVD risk reduction and may be useful in monitoring treatment response. View Full-Text
Keywords: statins; cholesterol; low-density lipoprotein cholesterol; cardiovascular disease; targeted lipidomics; lipid metabolism statins; cholesterol; low-density lipoprotein cholesterol; cardiovascular disease; targeted lipidomics; lipid metabolism
Show Figures

Figure 1

MDPI and ACS Style

Schooneveldt, Y.L.; Giles, C.; Keating, M.F.; Mellett, N.A.; Jurrjens, A.W.; Paul, S.; Calkin, A.C.; Meikle, P.J. The Impact of Simvastatin on Lipidomic Markers of Cardiovascular Risk in Human Liver Cells Is Secondary to the Modulation of Intracellular Cholesterol. Metabolites 2021, 11, 340. https://doi.org/10.3390/metabo11060340

AMA Style

Schooneveldt YL, Giles C, Keating MF, Mellett NA, Jurrjens AW, Paul S, Calkin AC, Meikle PJ. The Impact of Simvastatin on Lipidomic Markers of Cardiovascular Risk in Human Liver Cells Is Secondary to the Modulation of Intracellular Cholesterol. Metabolites. 2021; 11(6):340. https://doi.org/10.3390/metabo11060340

Chicago/Turabian Style

Schooneveldt, Yvette L., Corey Giles, Michael F. Keating, Natalie A. Mellett, Aaron W. Jurrjens, Sudip Paul, Anna C. Calkin, and Peter J. Meikle. 2021. "The Impact of Simvastatin on Lipidomic Markers of Cardiovascular Risk in Human Liver Cells Is Secondary to the Modulation of Intracellular Cholesterol" Metabolites 11, no. 6: 340. https://doi.org/10.3390/metabo11060340

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop