<> "The repository administrator has not yet configured an RDF license."^^ . <> . . . "Rev-erb agonist improves adverse cardiac \r\nremodeling and survival in myocardial \r\ninfarction through an anti-inflammatory \r\nmechanism"^^ . "As a leading cause of death and an increasing health burden worldwide, \r\nmyocardial infarction (MI) remains one of the most important clinical \r\nentities. After the onset of MI, the left ventricle (LV) undergoes a \r\ncontinuum of molecular, cellular, and extracellular responses that result in \r\nLV wall thinning, dilatation, and dysfunction (Thygesen et al., 2012). The \r\ncardiac healing and remodeling process after MI can be divided into four \r\nphases: the death of cardiomyocytes, acute inflammation, the formation of \r\ngranulation tissue, and scar formation (Figure 1). Acute inflammation \r\nusually occurs just after the onset of myocardial infarction. During this \r\nphase, neutrophils and monocytes are recruited into necrotic tissue, and \r\nthey release inflammatory cytokines and matrix metalloproteinase (MMP)\r\n(Liehn et al., 2011). Inflammatory cell infiltration and MMP production \r\nplay important roles in the degradation of necrotic debris and the \r\nsubsequent scar formation. However, excess inflammatory response and \r\nMMP overproduction are likely to induce adverse cardiac remodeling, \r\n\r\nleading to left ventricular dilatation, dysfunction, and cardiac rupture\r\n(Frangogiannis, 2015; Matsui et al., 2010). Despite the significant progress \r\nmade on therapeutic strategies for MI in last few decades, mortality and \r\nmorbidity remain high, and adverse cardiac remodeling after MI remains a \r\ncritical issue to be solved. Therefore, continuous improvement in \r\nmedications for the disease is still a major concern in global medical \r\nresearch.\r\nNuclear receptors (NRs) are members of a large superfamily and \r\nwidely considered as ligand-activated transcriptional factors. These were \r\noriginally found within cells that are responsible for sensing steroid and \r\nthyroid hormones and certain other molecules, and work with other \r\nproteins to regulate the expression of specific genes, thereby controlling the \r\ndevelopment, homeostasis, and metabolism of the organism (Chambon, \r\n2005; Evans, 2005). Nuclear receptors represent one of the most important\r\ntargets for therapeutic drug development, and many compounds targeted \r\nfor nuclear receptors have already been developed as marketable drugs, e.g. \r\nperoxisome proliferator-activated receptor α and γ activators. \r\nRev-erb belongs to a nuclear receptor superfamily, and contains two \r\nsubgroups, Rev-erb α (NR1D1) and β (NR1D2). Rev-erb α is highly \r\nexpressed in the liver, skeletal muscle, adipose tissue, heart and brain,\r\n\r\nparticipating in the development and circadian regulation of these tissues.\r\n(Solt et al., 2012). Rev-erb β displays a similar structure and has been \r\nimplicated in the control of lipid and glucose metabolism and circadian \r\nrhythm, collaborating extensively with Rev-erb α (Bugge et al., 2012).\r\nHeme was identified as a physiological ligand for Rev-erb receptor, which \r\nregulates their transcriptional activity (Figure 2). Moreover, Rev-erb α \r\ndisplays a hydrophobic interface that binds the corepressor N-CoR, making \r\nit a potent transcriptional repressor (Solt et al., 2012; Woldt et al., 2013).\r\nPrevious studies reported Rev-erb α regulated mitochondrial biogenesis in \r\nloss- and gain-of-function settings. Rev-erb α deficiency in skeletal muscle \r\nresulted in reduced mitochondrial content and ATP production through \r\ndeactivating AMPK-SIRT1–PGC1 signaling pathway (Woldt et al., 2103). \r\nRecently, SR9009 and SR9011 were developed as synthetic Rev-erb \r\nagonists, which facilitates Rev-erb α to recruit its corepressor NCoR and \r\nrepress downstream targets (Solt et al., 2012). From the results of the \r\nprevious studies using agonists, it has been identified that the nuclear \r\nreceptor Rev-erb α plays a pivotal role in the modulation of skeletal muscle \r\noxidative capacity by regulating mitochondrial biogenesis and autophagy, \r\nleading to increasing in exercise capacity (Woldt et al., 2013). Moreover, \r\nlong-term treatment with SR9009 was shown to reduce atherosclerotic \r\n\r\nplaque by decreasing the ratio of proinflammatory M1 macrophages to \r\nanti-inflammatory M2 macrophages in low-density lipoprotein (LDL) \r\nreceptor-deficient mice fed a Western diet (Sitaula et al., 2015). Therefore, \r\nRev-erb is expected to be a promising therapeutic target for metabolic \r\nsyndrome and atherosclerotic disease. However, little is known about the \r\nRev-erb agonist effect on the progression of MI and heart failure"^^ . "2018" . . . "University Of Tsukuba"^^ . . . "School of Comprehensive Human Science, Cardiovascular Medicine, University Of Tsukuba"^^ . . . . . . . . . "Endin"^^ . "Endin Nokik Stujanna"^^ . "Endin Endin Nokik Stujanna"^^ . . . . . . "Rev-erb agonist improves adverse cardiac \r\nremodeling and survival in myocardial \r\ninfarction through an anti-inflammatory \r\nmechanism (Text)"^^ . . . "Rev-erb agonist improves adverse cardiac \r\nremodeling and survival in myocardial \r\ninfarction through an anti-inflammatory \r\nmechanism (Other)"^^ . . . . . . "Rev-erb agonist improves adverse cardiac \r\nremodeling and survival in myocardial \r\ninfarction through an anti-inflammatory \r\nmechanism (Other)"^^ . . . . . . "Rev-erb agonist improves adverse cardiac \r\nremodeling and survival in myocardial \r\ninfarction through an anti-inflammatory \r\nmechanism (Other)"^^ . . . . . . "Rev-erb agonist improves adverse cardiac \r\nremodeling and survival in myocardial \r\ninfarction through an anti-inflammatory \r\nmechanism (Other)"^^ . . . . . "HTML Summary of #17280 \n\nRev-erb agonist improves adverse cardiac \nremodeling and survival in myocardial \ninfarction through an anti-inflammatory \nmechanism\n\n" . "text/html" . . . "R Medicine"@en . .