title: Mechanistic Role of MicroRNAs in Coupling Lipid Metabolism and Atherosclerosis.
abstract: MicroRNAs (miRNAs, miRs) represent a group of powerful and versatile posttranscriptional regulators of gene expression being involved in the fine control of a plethora of physiological and pathological processes. Besides their well-established crucial roles in the regulation of cell cycle, embryogenesis or tumorigenesis, these tiny molecules have also been shown to participate in the regulation of lipid metabolism. In particular, miRs orchestrate cholesterol and fatty acids synthesis, transport, and degradation and low-density and high-density lipoprotein (LDL and HDL) formation. It is thus not surprising that they have also been reported to affect the development and progression of several lipid metabolism-related disorders including liver steatosis and atherosclerosis. Mounting evidence suggests that miRs might represent important "posttranscriptional hubs" of lipid metabolism, which means that one miR usually targets 3'-untranslated regions of various mRNAs that are involved in different steps of one precise metabolic/signaling pathway, e.g., one miR targets mRNAs of enzymes important for cholesterol synthesis, degradation, and transport. Therefore, changes in the levels of one key miR affect various steps of one pathway, which is thereby promoted or inhibited. This makes miRs potent future diagnostic and even therapeutic tools for personalized medicine. Within this chapter, the most prominent microRNAs involved in lipid metabolism, e.g., miR-27a/b, miR-33/33*, miR-122, miR-144, or miR-223, and their intracellular and extracellular functions will be extensively discussed, in particular focusing on their mechanistic role in the pathophysiology of atherosclerosis. Special emphasis will be given on miR-122, the first microRNA currently in clinical trials for the treatment of hepatitis C and on miR-223, the most abundant miR in lipoprotein particles.
authors.affiliation: 2nd Department of Internal Medicine, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic. jnmedved@seznam.cz.|Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5-building A18, Brno, 62500, Czech Republic. jnmedved@seznam.cz.|Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5-building A20, Brno, 62500, Czech Republic. jnmedved@seznam.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Novák
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5-building A20, Brno, 62500, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Olejníčková
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5-building A20, Brno, 62500, Czech Republic.
authors.forename: Nikola
authors.initials: N
authors.lastname: Tkáčová
authors.affiliation: Columbia University Medical Center, New York Presbyterian Hospital —Manhattan, New York, NY, USA; “Federico II” University Hospital, Naples, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Santulli
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D006801:Humans; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000235:genetics / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000235:genetics / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*
chemical_list: D002784:Cholesterol; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D035683:MicroRNAs; C531907:MIRN122 microRNA, human; C525067:MIR223, human; C550416:MIRN33a microRNA, human
keywords: Atherosclerosis; Cholesterol; HDL; LDL; Lipid metabolism; miR-122; miR-223; miR-33