Pravastatin‐induced changes in expression of long non‐coding and coding RNAs in endothelial cells
Open Access
- 28 December 2020
- journal article
- research article
- Published by Wiley in Physiological Reports
- Vol. 9 (1), e14661
- https://doi.org/10.14814/phy2.14661
Abstract
Objective Atherosclerosis is the main cause of the cardiovascular disease (CVD). Elevated blood cholesterol and inflammation of the endothelium are two major mechanisms contributing to the establishment of atherosclerotic plaques. Statins, such as pravastatin, are blood‐cholesterol lowering drugs commonly prescribed for patients with or at risk for CVDs. In addition to lowering blood cholesterols, statins have recently been shown to improve endothelial function in both hyper‐ and normocholesterolemic patients with atherosclerosis. To understand the molecular mechanisms underlying the endothelial function improvement by statins, we assessed the RNA profile of pravastatin‐treated endothelial cells, particularly their mRNAs and long non‐coding RNAs (lncRNAs). Methods Human umbilical vein endothelial cells (HUVECs) treated with pravastatin (10 µM) for 24 hr were profiled for lncRNAs and mRNAs using the Arraystar Human lncRNA Expression Microarray V3.0. Results Of the 30,584 different lncRNAs screened, 95 were significantly upregulated, while 86 were downregulated in HUVECs responding to pravastatin. LINC00281 and BC045663 were the most upregulated (~8‐fold) and downregulated (~3.5‐fold) lncRNAs, respectively. Of the 26,106 different mRNAs screened in the pravastatin‐treated HUVEC samples, 190 were significantly upregulated, while 90 were downregulated. Assigning the differentially expressed genes by bioinformatics into functional groups revealed their molecular signaling involvement in the following physiological processes: osteoclast differentiation, Rap1 signaling pathway, hematopoiesis, immunity, and neurotrophin signaling pathway. Conclusions This is the first lncRNA and mRNA expression profiling of pravastatin‐mediated changes in human endothelial cells. Our results reveal potential novel targets and mechanisms for pravastatin‐mediated vascular protection in atherosclerosis.Funding Information
- Heart and Stroke Foundation of Canada (2018/19 National New Investigator Award)
- Canadian Institutes of Health Research (FRN # 153216)
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