Abstract
Objective: The beneficial effects of icariin (ICA) in ameliorating atherosclerosis (AS) are well known, but the underlying protective mechanism has not been fully elucidated. The present study aimed to investigate altered long noncosing RNA (lncRNA) and mRNA expression profiles in ApoE−/− mice after ICA treatment.Method: The atherosclerotic plaque area was evaluated on high-fat diet (HFD)-induced ApoE−/− mice treated with either ICA or vehicle. LncRNA and mRNA integrated microarrays was performed on aortic tissues. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were utilized to explore the significant function and pathway of the differentially expressed (DE) mRNAs, global signal transduction network were constructed to select key mRNAs, and lncRNA–mRNA co-expression network was built to find out the interactions between lncRNA and mRNA. Quantitative real-time PCR (qPCR) was used to further validate the expressions of selected lncRNAs and mRNAs.Results: Administration of ICA significantly reduced plaque size after 12 weeks (P<0.05). A total of 1512 DE lncRNAs and 2059 DE mRNAs were identified. The mRNAs: protein kinase C, β (Prkcb), Cyp2c65, Mapk10, Calmodulin 5 (Calm5), Calmodulin-like 3 (Calml3) and Camk4 were selected as hub mRNAs, the correlated lncRNAs in co-expression network were identified as important regulatory lncRNAs. The identified target pairs such as lncRNA-NONMMUT000659/Prkcb may play critical roles in AS development mediated by ICA.Conclusion: Taken together, our study highlights a panel of DE lncRNAs and mRNAs that could explain the molecular mechanism of ICA’s anti-atherosclerotic effects. The work lays a foundation for subsequent genes functional researches, which could contribute to provide new therapeutic targets for AS.
Highlights
Atherosclerosis (AS), characterized by progressing atherosclerotic plaques formation and luminal narrowing of arteries, underpins coronary artery disease (CAD) with high mortality worldwide [1]
According to the key mRNAs selected above in global signal transduction network, we found that long noncosing RNA (lncRNA) NONMMUT000659 and Ighv8-14 were positively correlated with protein kinase C (Prkcb), lncRNA NONMMUT031625 was positively correlated with Cyp2c65, lncRNA Gm2904 was negatively correlated with Mapk10
We explored the distinct expression profiles of lncRNAs as well as mRNAs in ICA treatment and model ApoE−/− mice using microarray technology, suggesting a large amount of lncRNAs and mRNAs might be linked to the protective effect of ICA
Summary
Atherosclerosis (AS), characterized by progressing atherosclerotic plaques formation and luminal narrowing of arteries, underpins coronary artery disease (CAD) with high mortality worldwide [1]. Despite great advances in therapeutic agents such as statin, CAD remains a healthcare and economic burden. Potential adverse effects of statin application make several patients stop receiving statin therapy [2,3]. Identifying novel curative strategies as well as new biomarkers for therapeutic targeting in AS are desired. Medicinal herbs emerge as alternative and complementary options with high efficiency and less side effects for AS management [4]. Herba Epimedii has been documented in the Chinese Pharmacopoeia (2015) as a traditional Chinese herb has extensive clinical indications [5]. Icariin (ICA) (C33H40O15; License 4.0 (CC BY)
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