The role of endothelial mechanosensitive genes in atherosclerosis and omics approaches

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, miRNA-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.

Systems biology analysis of longitudinal functional response of endothelial cells to shear stress

“…Inflammation. ECs exposed to OS exhibit proinflammatory phenotypes through the activation of NF-κB and the up-regulation of several proinflammatory cytokines (13,44). The temporally varying expression profiles of NF-κB targets and canonical proinflammatory genes show a sharp OS vs. PS up-regulation between hours 2 and 6 ( Fig.…”

“…The mechanisms of EC response to distinct shear stresses have been inferred primarily from signaling and transcriptional measurements (12)(13)(14)(15)(16). Transcriptional measurements have been carried out at specific time points after the application of stress, providing only snapshot profiles of altered gene expression (14,17,18).…”

Mouse models of atherosclerosis: a historical perspective and recent advances

“…Development of atherosclerosis is influenced by a number of genes, which interact with each other and the environment to affect the disease phenotype [47]. Manipulation can take place for single genes, and indeed in a time-dependent manner, which permits the elucidation of the molecular mechanisms operating in different phase of plaque evolution, whilst the manipulation of gene expression in specific cell types has increased our understanding of the contributions of different immune cells to atherosclerosis.…”

Impact of the “Omics Sciences” in Medicine: New Era for Integrative Medicine

“…Protein-protein interaction [31] Hypertension [32] Renal diseases [33,34] Tuberculosis [35] Cardiovascular homeostasis [36] Endocrine processes [37] Atherosclerosis [38] Chronic pulmonary obstruction [39] Cancer [40][41][42][43][44] Virus infection [45] Arthritis [46] Doping [47] Process/Disease Protein-protein interaction [31] Hypertension [32] Renal diseases [33,34] Tuberculosis [35] Cardiovascular homeostasis [36] Endocrine processes [37] Atherosclerosis [38] Chronic pulmonary obstruction [39] Cancer [40][41][42][43][44] Virus infection [45] Arthritis [46] Doping [47] Citation: Plaza Table 1). This technical-analytical boom, among others, led to the development of the called "human genome project" for instance (Https://www.genome.gov/10001772/allabout-the--human-genome-project-hgp/).…”