The role of endothelial mechanosensitive genes in atherosclerosis and omics approaches

• Authors: Rachel D. Simmons, Georgia Institute of Technology; Sandeep Kumar, Emory University; Hanjoong Jo, Emory University
• Journal Title: Archives of Biochemistry and Biophysics
• Volume: Volume 591
• Publisher: Elsevier | 2016-02-01, Pages 111-131
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.abb.2015.11.005
• Subjects: Engineering, Biomedical
• Keywords: Science & Technology; Life Sciences & Biomedicine; Biochemistry & Molecular Biology; Biophysics; Mechanosensitive; Blood flow; Shear stress; Endothelial cells; Atherosclerosis; Genomics; Epigenomics; miRNomics; Metabolomics; WALL SHEAR-STRESS; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; KRUPPEL-LIKE FACTOR-2; CELL-ADHESION MOLECULE-1; SMOOTH-MUSCLE-CELLS; CORONARY-ARTERY-DISEASE; HEPARAN-SULFATE PROTEOGLYCANS; PROTEIN-KINASE-C; E-DEFICIENT MICE

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.