Abstract
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.
Highlights
Atherosclerosis is an arterial inflammatory process of atheroma plaque formation initiated by the erroneous accumulation of apolipoprotein B-containing cholesterol, low-density lipoprotein cholesterol (LDL-C), in subendothelial space of arteries [1]
Given clinical studies have showed that statins would confer less risk reduction of cardiovascular diseases in individuals with high serum C-reactive protein (CRP) levels [11,12], anti-inflammatory treatment is emerging as a complement to lipid-lowering treatment in Atherosclerotic cardiovascular disease (ASCVD) patients [13]
There was no difference in CRP changes between the pitavastatin or atorvastatin subgroup (P = 0.67, 0.34, respectively)
Summary
Atherosclerosis is an arterial inflammatory process of atheroma plaque formation initiated by the erroneous accumulation of apolipoprotein B-containing cholesterol, low-density lipoprotein cholesterol (LDL-C), in subendothelial space of arteries [1]. Known as an efficacious treatment for hypercholesterolemia, statins lower the risk for major vascular events by 23% per 1 mmol/l LDL-C reduction [4]. The immune cells involved in inflammation progression and resolution of atheroma plaques are mainly from peripheral blood mononuclear cells (PBMCs), including monocytes, lymphocytes, and dendritic cells [6]. Given clinical studies have showed that statins would confer less risk reduction of cardiovascular diseases in individuals with high serum C-reactive protein (CRP) levels [11,12], anti-inflammatory treatment is emerging as a complement to lipid-lowering treatment in ASCVD patients [13]. How to reliably identify ASCVD patients with discernible inflammation in atheroma plaques could be fundamental to implementing anti-inflammatory treatment in clinical setting
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
