miRNAs from Plasma Extracellular Vesicles Are Signatory Noninvasive Prognostic Biomarkers against Atherosclerosis in LDLr-/-Mice

被引:7
|
作者
Zhai, Ke-Feng [1 ,2 ,3 ,4 ]
Duan, Hong [2 ]
Shi, Yan [2 ]
Zhou, Ya-Ru [2 ]
Chen, Yuan [2 ]
Zhang, Yao-Shuai [5 ]
Gong, Zi-Peng [4 ]
Cao, Wen-Gen [2 ]
Wu, Jia [1 ]
Wang, Jun-Jun [1 ]
机构
[1] Nanjing Univ, Jinling Hosp, Dept Clin Lab, Med Sch, Nanjing 210002, Peoples R China
[2] Suzhou Univ, Suzhou Engn & Technol Res Ctr Nat Med & Funct Foo, Sch Biol & Food Engn, 49 Bianhe Rd, Suzhou 234000, Peoples R China
[3] Guangxi Normal Univ, State Key Lab Chem & Mol Engn Med Resources Guang, Guilin 541004, Peoples R China
[4] Guizhou Med Univ, Engn Res Ctr Dev & Applicat Ethn Med & TCM, State Key Lab Funct & Applicat Med Plants, Guizhou Prov Key Lab Pharmaceut,Minist Educ, Guiyang 550004, Peoples R China
[5] Bengbu Med Coll, Fac Pharm, Bengbu 233030, Peoples R China
基金
安徽省自然科学基金; 中国国家自然科学基金;
关键词
MICRORNAS; INFLAMMATION;
D O I
10.1155/2022/6887192
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Circular microRNAs (miRNAs) have become central in pathophysiological conditions of atherosclerosis (AS). However, the biomarkers for diagnosis and therapeutics against AS are still unclear. The atherosclerosis models in low-density lipoprotein receptor deficiency (LDLr-/-) mice were established with a high-fat diet (HFD). The extraction kit isolated extracellular vesicles from plasma. Total RNAs were extracted from LDLr-/- mice in plasma extracellular vesicles. Significantly varying miRNAs were detected by employing Illumina HiSeq 2000 deep sequencing technology. Target gene predictions of miRNAs were employed by related software that include RNAhybrid, TargetScan, miRanda, and PITA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) further analyzed the intersection points of predicted results. The results showed that the HFD group gradually formed atherosclerotic plaques in thoracic aorta compared with the control group. Out of 17, 8 upregulated and 9 downregulated miRNAs with a significant difference were found in the plasma extracellular vesicles that were further cross-examined by sequencing and bioinformatics analysis. Focal adhesion and Ras signaling pathway were found to be the most closely related pathways through GO and KEGG pathway analyses. The 8 most differentially expressed up- and downregulated miRNAs were further ascertained by TaqMan-based qRT-PCR. TaqMan-based qRT-PCR and in situ hybridization further validated the most differentially expressed miRNAs (miR-378d, miR-181b-5p, miR-146a-5p, miR-421-3p, miR-350-3p, and miR-184-3p) that were consistent with deep sequencing analysis suggesting a promising potential of utility to serve as diagnostic biomarkers against AS. The study gives a comprehensive profile of circular miRNAs in atherosclerosis and may pave the way for identifying biomarkers and novel targets for atherosclerosis.
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页数:12
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