title: Emerging topic: flow-related epigenetic regulation of endothelial phenotype through DNA methylation.
abstract: Atherosclerosis is a multi-focal disease; it is associated with arterial curvatures, asymmetries and branches/bifurcations where non-uniform arterial geometry generates patterns of blood flow that are considerably more complex than elsewhere, and are collectively referred to as disturbed flow. Such regions are predisposed to atherosclerosis and are the sites of 'athero-susceptible' endothelial cells that express regionally different cell phenotypes than endothelium in nearby athero-protected locations. The regulatory hierarchy of endothelial function includes control at the epigenetic level. MicroRNAs and histone modifications are established epigenetic regulators that respond to disturbed flow. However, very recent reports have linked transcriptional regulation by DNA methylation to endothelial gene expression in disturbed flow in vivo and in vitro. We outline these in the context of site-specific atherosusceptibility mediated by local hemodynamics.
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, Perelman School of Medicine, 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 Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Manduchi
authors.affiliation: Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Stoeckert
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; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000235:genetics*; D006801:Humans; D010641:Phenotype
keywords: Atherosclerosis; DNA methylation; Endothelium; Epigenetics; Hemodynamics