title: Endothelial epigenetics in biomechanical stress: disturbed flow-mediated epigenomic plasticity in vivo and in vitro.
abstract: Arterial endothelial phenotype is regulated by local hemodynamic forces that are linked to regional susceptibility to atherogenesis. A complex hierarchy of transcriptional, translational, and post-translational mechanisms is greatly influenced by the characteristics of local arterial shear stress environments. We discuss the emerging role of localized disturbed blood flow on epigenetic mechanisms of endothelial responses to biomechanical stress, including transcriptional regulation by proximal promoter DNA methylation, and post-transcriptional and translational regulation of gene and protein expression by chromatin remodeling and noncoding RNA-based mechanisms. Dynamic responses to flow characteristics in vivo and in vitro include site-specific differentially methylated regions of swine and mouse endothelial methylomes, histone marks regulating chromatin conformation, microRNAs, and long noncoding RNAs. Flow-mediated epigenomic responses intersect with cis and trans factor regulation to maintain endothelial function in a shear-stressed environment and may contribute to localized endothelial dysfunctions that promote atherosusceptibility.
authors.affiliation: From the Institute for Medicine and Engineering (Y-Z.J., J.M.J., P.F.D.) and Departments of Pathology and Laboratory Medicine (Y-Z.J., J.M.J., P.F.D.), Bioengineering (P.F.D.), and Genetics (E.M.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Yi-Zhou
authors.initials: YZ
authors.lastname: Jiang
authors.affiliation: From the Institute for Medicine and Engineering (Y-Z.J., J.M.J., P.F.D.) and Departments of Pathology and Laboratory Medicine (Y-Z.J., J.M.J., P.F.D.), Bioengineering (P.F.D.), and Genetics (E.M.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Manduchi
authors.affiliation: From the Institute for Medicine and Engineering (Y-Z.J., J.M.J., P.F.D.) and Departments of Pathology and Laboratory Medicine (Y-Z.J., J.M.J., P.F.D.), Bioengineering (P.F.D.), and Genetics (E.M.), Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Jiménez
authors.affiliation: From the Institute for Medicine and Engineering (Y-Z.J., J.M.J., P.F.D.) and Departments of Pathology and Laboratory Medicine (Y-Z.J., J.M.J., P.F.D.), Bioengineering (P.F.D.), and Genetics (E.M.), Perelman School of Medicine, University of Pennsylvania, Philadelphia. pfd@mail.med.upenn.edu.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Davies
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics* / Q000503:physiopathology*; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D004730:Endothelium, Vascular / Q000503:physiopathology*; D044127:Epigenesis, Genetic; D005801:Genes, Homeobox / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D035683:MicroRNAs / Q000502:physiology; D010641:Phenotype; D046188:Protein Modification, Translational; D062085:RNA, Long Noncoding / Q000502:physiology; D012097:Repressor Proteins / Q000378:metabolism; D013314:Stress, Mechanical; D014158:Transcription, Genetic
chemical_list: C411744:DMAP1 protein, human; C000717967:DNMT3A protein, human; D006657:Histones; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A
keywords: DNA methylation; atherogenesis; chromatin assembly and disassembly; epigenomics; hemodynamics
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