Profiling of Primary and Mature miRNA Expression in Atherosclerosis-Associated Cell Types
Open Access
- 1 July 2021
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 41 (7), 2149-2167
- https://doi.org/10.1161/atvbaha.121.315579
Abstract
Download figure Download PowerPoint Objective: Atherosclerosis is the underlying cause of most cardiovascular diseases. The main cell types associated with disease progression in the vascular wall are endothelial cells, smooth muscle cells, and macrophages. Although their role in atherogenesis has been extensively described, molecular mechanisms underlying gene expression changes remain unknown. The objective of this study was to characterize microRNA (miRNA)-related regulatory mechanisms taking place in the aorta during atherosclerosis. Approach and Results: We analyzed the miRNA expression changes in primary human aortic endothelial cells and human umbilical vein endothelial cells, human aortic smooth muscle cells, and macrophages (CD14+) under various proatherogenic stimuli by integrating GRO-seq, miRNA-seq, and RNA-seq data. Despite the highly cell-type-specific expression of multi-variant primary miRNAs, the majority of mature miRNAs were found to be common to all cell types and dominated by 2 to 5 abundant miRNA species. We demonstrate that transcription contributes significantly to the mature miRNA levels although this is dependent on miRNA stability. An analysis of miRNA effects in relation to target mRNA pools highlighted pathways and targets through which miRNAs could affect atherogenesis in a cell-type-dependent manner. Finally, we validate miR-100-5p as a cell-type specific regulator of inflammatory and HIPPO-YAP/TAZ-pathways. Conclusions: This integrative approach allowed us to characterize miRNA dynamics in response to a proatherogenic stimulus and identify potential mechanisms by which miRNAs affect atherogenesis in a cell-type-specific manner.Keywords
This publication has 105 references indexed in Scilit:
- An integrated encyclopedia of DNA elements in the human genomeNature, 2012
- High-throughput assessment of microRNA activity and function using microRNA sensor and decoy librariesNature Methods, 2012
- Reprogramming transcription by distinct classes of enhancers functionally defined by eRNANature, 2011
- Metabolic labeling of RNA uncovers principles of RNA production and degradation dynamics in mammalian cellsNature Biotechnology, 2011
- Simple Combinations of Lineage-Determining Transcription Factors Prime cis-Regulatory Elements Required for Macrophage and B Cell IdentitiesMolecular Cell, 2010
- Inhibition of eukaryotic translation elongation by cycloheximide and lactimidomycinNature Chemical Biology, 2010
- The knockout of miR-143 and -145 alters smooth muscle cell maintenance and vascular homeostasis in mice: correlates with human diseaseCell Death & Differentiation, 2009
- miR-145 and miR-143 regulate smooth muscle cell fate and plasticityNature, 2009
- miR-126 Regulates Angiogenic Signaling and Vascular IntegrityDevelopmental Cell, 2008
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005