title: Flow signaling and atherosclerosis.
abstract: Atherosclerosis rarely develops in the region of arteries exposed to undisturbed flow (u-flow, unidirectional flow). Instead, atherogenesis occurs in the area exposed to disturbed flow (d-flow, multidirectional flow). Based on these general pathohistological observations, u-flow is considered to be athero-protective, while d-flow is atherogenic. The fact that u-flow and d-flow induce such clearly different biological responses in the wall of large arteries indicates that these two types of flow activate each distinct intracellular signaling cascade in vascular endothelial cells (ECs), which are directly exposed to blood flow. The ability of ECs to differentially respond to the two types of flow provides an opportunity to identify molecular events that lead to endothelial dysfunction and atherosclerosis. In this review, we will focus on various molecular events, which are differentially regulated by these two flow types. We will discuss how various kinases, ER stress, inflammasome, SUMOylation, and DNA methylation play roles in the differential flow response, endothelial dysfunction, and atherosclerosis. We will also discuss the interplay among the molecular events and how they coordinately regulate flow-dependent signaling and cellular responses. It is hoped that clear understanding of the way how the two flow types beget each unique phenotype in ECs will lead us to possible points of intervention against endothelial dysfunction and cardiovascular diseases.
authors.affiliation: Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Unit 1101, 1515 Holcombe Blvd., Houston, Texas, 77030-4009, USA. nle3@mdanderson.org.
authors.forename: Nhat-Tu
authors.initials: NT
authors.lastname: Le
authors.affiliation: Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Unit 1101, 1515 Holcombe Blvd., Houston, Texas, 77030-4009, USA.
authors.forename: Uday G
authors.initials: UG
authors.lastname: Sandhu
authors.affiliation: Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Unit 1101, 1515 Holcombe Blvd., Houston, Texas, 77030-4009, USA.
authors.forename: Raymundo A
authors.initials: RA
authors.lastname: Quintana-Quezada
authors.affiliation: Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Unit 1101, 1515 Holcombe Blvd., Houston, Texas, 77030-4009, USA.
authors.forename: Nguyet Minh
authors.initials: NM
authors.lastname: Hoang
authors.affiliation: Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Unit 1101, 1515 Holcombe Blvd., Houston, Texas, 77030-4009, USA.
authors.forename: Keigi
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Department of Cardiology, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Unit 1101, 1515 Holcombe Blvd., Houston, Texas, 77030-4009, USA.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Abe
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000473:pathology*; D050197:Atherosclerosis / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D059865:Endoplasmic Reticulum Stress; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D048054:Mitogen-Activated Protein Kinase 7 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000378:metabolism; D012039:Regional Blood Flow; D015398:Signal Transduction; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism; D058207:Sumoylation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D058847:Inflammasomes; D051782:Sterol Regulatory Element Binding Protein 2; D016159:Tumor Suppressor Protein p53; D011493:Protein Kinase C; D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11
keywords: AMPK; DNA methylation; DRP-1; ER stress; ERK5; HATs and HDACs; MAP kinase; NEMO; PKC family; PPARs; SENP2; SUMOylation; p90RSK