https://scholars.lib.ntu.edu.tw/handle/123456789/514726
標題: | Statin-induced microRNAome alterations modulating inflammation pathways of peripheral blood mononuclear cells in patients with hypercholesterolemia | 作者: | HUNG-JU LIN SUNG-LIANG YU TA-CHEN SU Hsu, Hsiu-Ching MING-FONG CHEN Lee, Yuan-Teh KUO-LIONG CHIEN TZU-PIN LU |
公開日期: | 2020 | 出版社: | NLM (Medline) | 卷: | 40 | 期: | 9 | 來源出版物: | Bioscience reports | 摘要: | Statins inhibit cholesterol biogenesis and modulate atheroma inflammation to reduce cardiovascular risks. Promoted by immune and non-immune cells, serum C-reactive protein (CRP) might be a biomarker suboptimal to assess inflammation status. Although it has been reported that statins modulated inflammation via microRNAs (miRNAs), evidence remains lacking on comprehensive profiling of statin-induced miRNAome alterations in immune cells. We recruited 19 hypercholesterolemic patients receiving 2 mg/day pitavastatin and 15 ones receiving 10 mg/day atorvastatin treatment for 12 weeks, and performed microarray-based profiling of 1733 human mature miRNAs in peripheral blood mononuclear cells (PBMCs) before and after statin treatment. Differentially expressed miRNAs were determined if their fold changes were >1.50 or <0.67, after validated using quantitative polymerase chain reaction (qPCR). The miRSystem and miTALOS platforms were utilized for pathway analysis. Of the 34 patients aged 63.7 +- 6.2 years, 27 were male and 19 were with coronary artery disease. We discovered that statins induced differential expressions of miR-483-5p, miR-4667-5p, miR-1244, and miR-3609, with qPCR-validated fold changes of 1.74 (95% confidence interval, 1.33–2.15), 1.61 (1.25–1.98), 1.61 (1.01–2.21), and 1.68 (1.19–2.17), respectively. The fold changes of the four miRNAs were not correlated with changes of low-density-lipoprotein cholesterol or CRP, after sex, age, and statin type were adjusted. We also revealed that RhoA and transforming growth factor-β signaling pathways might be regulated by the four miRNAs. Given our findings, miRNAs might be involved in statin-induced inflammation modulation in PBMCs, providing likelihood to assess and reduce inflammation in patients with atherosclerotic cardiovascular diseases. ? 2020 The Author(s). |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85091323821&doi=10.1042%2fBSR20201885&partnerID=40&md5=268fffcb7e879d1e8a95e189750ca478 https://scholars.lib.ntu.edu.tw/handle/123456789/514726 |
ISSN: | 1573-4935 | DOI: | 10.1042/BSR20201885 | SDG/關鍵字: | atorvastatin; C reactive protein; high density lipoprotein cholesterol; low density lipoprotein cholesterol; microRNA; microRNA 1244; microRNA 3609; microRNA 4667 5p; microRNA 483 5p; pitavastatin; RhoA guanine nucleotide binding protein; transforming growth factor beta; unclassified drug; atorvastatin; hydroxymethylglutaryl coenzyme A reductase inhibitor; low density lipoprotein cholesterol; microRNA; pitavastatin; quinoline derivative; adult; age; antiinflammatory activity; Article; clinical article; controlled study; coronary artery atherosclerosis; coronary artery disease; female; human; human cell; hypercholesterolemia; hypertension; immunocompetent cell; male; microarray analysis; middle aged; non insulin dependent diabetes mellitus; peripheral blood mononuclear cell; real time polymerase chain reaction; RNA analysis; RNA fingerprinting; sex; smoking; TGF beta signaling; aged; atherosclerotic plaque; blood; clinical trial; complication; drug effect; gene expression profiling; gene expression regulation; genetics; hypercholesterolemia; immunology; metabolism; mononuclear cell; multicenter study; randomized controlled trial; Taiwan; Aged; Atorvastatin; Cholesterol, LDL; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Leukocytes, Mononuclear; Male; MicroRNAs; Middle Aged; Plaque, Atherosclerotic; Quinolines; Taiwan |
顯示於: | 醫學系 |
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