title: Biofluids, cell mechanics and epigenetics: Flow-induced epigenetic mechanisms of endothelial gene expression.
abstract: Epigenetics is the regulation of gene expression (transcription) in response to changes in the cell environment through genomic modifications that largely involve the non-coding fraction of the human genome and that cannot be attributed to modification of the primary DNA sequence. Epigenetics is dominant in establishing cell fate and positioning during programmed embryonic development. However the same pathways are used by mature postnatal and adult mammalian cells during normal physiology and are implicated in disease mechanisms. Recent research demonstrates that blood flow and pressure are cell environments that can influence transcription via epigenetic pathways. The principal epigenetic pathways are chemical modification of cytosine residues of DNA (DNA methylation) and of the amino tails of histone proteins associated with DNA in nucleosomes. They also encompass the post-transcriptional degradation of mRNA transcripts by non-coding RNAs (ncRNA). In vascular endothelium, epigenetic pathways respond to temporal and spatial variations of flow and pressure, particularly hemodynamic disturbed blood flow, with important consequences for gene expression. The biofluid environment is linked by mechanotransduction and solute transport to cardiovascular cell phenotypes via signaling pathways and epigenetic regulation for which there is an adequate interdisciplinary infrastructure with robust tools and methods available. Epigenetic mechanisms may be less familiar than acute genomic signaling to Investigators at the interface of biofluids, biomechanics and cardiovascular biology. Here we introduce a biofluids / cellular biomechanics readership to the principal epigenetic pathways and provide a contextual overview of endothelial epigenetic plasticity in the regulation of flow-responsive transcription.
authors.affiliation: Institute for Medicine and Engineering, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Bioengineering,University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: pfd@mail.med.upenn.edu.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Davies
authors.affiliation: Department of Computational Genetics Laboratory, Institute for Biomedical Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Manduchi
authors.affiliation: Institute for Medicine and Engineering, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Jiménez
authors.affiliation: Institute for Medicine and Engineering, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Yi-Zhou
authors.initials: YZ
authors.lastname: Jiang
mesh_terms: D000818:Animals; D001775:Blood Circulation; D019175:DNA Methylation; D042783:Endothelial Cells / Q000378:metabolism* / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology; D044127:Epigenesis, Genetic; D015870:Gene Expression; D006801:Humans
keywords: Disturbed blood flow; Endothelial phenotype; Epigenetics; Gene transcription; Hemodynamics; Mechanotransduction