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- W2950354911 abstract "Objective: Evidence is accumulating that microRNAs (miRNAs), members of the non-coding RNA family, may be effective biomarkers and therapeutic targets in atherosclerosis. The aim of this study was to identify novel miRNA expression patterns underlying vascular inflammation and oxidative stress associated with atheroma formation in human and experimental atherosclerosis. Design and method: Human non-atherosclerotic (superior thyroid artery) and atherosclerotic (carotid artery) arterial specimens, ApoE-/- mice, and in vitro polarized pro-, and anti-inflammatory mouse macrophages (Mac) were used. Male ApoE-/- mice were maintained on normal (ND) or high-fat cholesterol rich (HD) diet for 6 months to accelerate de development of advanced atherosclerotic lesions along the aorta. Atherosclerotic lesions were analyzed by Oil Red O staining and immunohistochemistry (markers of immune cell infiltration, CD45, CD68). Human and mouse miRCURY LNA™ miRNome real-time PCR panels were employed to determine the expression pattern of 752 different miRNAs. Microarray-based (Agilent SurePrint G3 Human/Mouse gene Expression v2 8x60K) genome-wide gene expression profiling was done to determine the ratio between a specific miRNA and the expression level of its predicted mRNA target. miRNA target prediction tools were used (miRanda, MiRBase, miRWalk, Target Scan, etc). Results: miRNA expression profiling revealed that 272 miRNAs are significantly up-regulated and 224 down-regulated in the atherosclerotic aorta of ApoE-/- (HD) mice as compared to values obtained for ApoE-/- (ND) animals. A cluster of 49 miRNAs with upregulated levels in atherosclerotic aorta of mice were detected in cultured pro-inflammatory mouse Mac as compared to resting Mac. In cultured anti-inflammatory Mac, the augmented expression of 63 miRNA was detected. Similarly regulated (up/down) homologous miRNAs were determined in both human and mouse atherosclerotic tissues. Candidate miRNAs linked to vascular inflammation and oxidative stress in atherosclerosis were predicted by in silico analysis. Conclusions: We found new miRNA panels reporting information about key pathological processes linked to atheroma formation such as inflammation and oxidative stress in both human and experimental atherosclerosis. The data of this study point to the novel atherosclerotic tissue-expressed miRNAs as potential biomarkers and/or therapeutic targets in atherosclerosis-related cardiovascular disorders." @default.
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- W2950354911 date "2019-07-01" @default.
- W2950354911 modified "2023-10-14" @default.
- W2950354911 title "IDENTIFICATION OF NOVEL MICRORNAS ASSOCIATED ATHEROSCLEROTIC LESION FORMATION IN THE AORTA OF HYPERCHOLESTEROLEMIC APOE-/- MICE" @default.
- W2950354911 doi "https://doi.org/10.1097/01.hjh.0000573644.32078.21" @default.
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