The role of endothelial mechanosensitive genes in atherosclerosis and omics approaches

• Type of Material: Article
• Authors: Rachel D. Simmons, Georgia Institute of Technology; Sandeep Kumar, Emory University; Hanjoong Jo, Emory University
• Language: English
• Date: 2016-02-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.abb.2015.11.005
• Title of Journal or Parent Work: Archives of Biochemistry and Biophysics
• ISSN: 0003-9861
• Volume: 591
• Start Page: 111
• End Page: 131
• Grant/Funding Information: This work was supported by funding from National Institutes of Health grants HL119798, HL113451, HL095070 and HL124879 to HJ.
• Keywords: Shear stress; E-DEFICIENT MICE; SMOOTH-MUSCLE-CELLS; CORONARY-ARTERY-DISEASE; Atherosclerosis; Genomics; NITRIC-OXIDE SYNTHASE; Metabolomics; Epigenomics; PROTEIN-KINASE-C; Endothelial cells; Life Sciences & Biomedicine; HEPARAN-SULFATE PROTEOGLYCANS; Science & Technology; NF-KAPPA-B; WALL SHEAR-STRESS; Mechanosensitive; KRUPPEL-LIKE FACTOR-2; miRNomics; Blood flow; Biochemistry & Molecular Biology; Biophysics; CELL-ADHESION MOLECULE-1
• Research Categories: Engineering, Biomedical

Abstract

Atherosclerosis is the leading cause of morbidity and mortality in the U.S., and is a multifactorial disease that preferentially occurs in regions of the arterial tree exposed to disturbed blood flow. The detailed mechanisms by which d-flow induces atherosclerosis involve changes in the expression of genes, epigenetic patterns, and metabolites of multiple vascular cells, especially endothelial cells. This review presents an overview of endothelial mechanobiology and its relation to the pathogenesis of atherosclerosis with special reference to the anatomy of the artery and the underlying fluid mechanics, followed by a discussion of a variety of experimental models to study the role of fluid mechanics and atherosclerosis. Various in vitro and in vivo models to study the role of flow in endothelial biology and pathobiology are discussed in this review. Furthermore, strategies used for the global profiling of the genome, transcriptome, miR-nome, DNA methylome, and metabolome, as they are important to define the biological and pathophysiological mechanisms of atherosclerosis. These "omics" approaches, especially those which derive data based on a single animal model, provide unprecedented opportunities to not only better understand the pathophysiology of atherosclerosis development in a holistic and integrative manner, but also to identify novel molecular and diagnostic targets.