title: Therapeutic regulation of cardiac fibroblast function: targeting stress-activated protein kinase pathways.
abstract: Cardiac fibroblasts are key players in the myocardial remodeling process and respond to myocardial damage or dysfunction by adopting a myofibroblast phenotype and undergoing increased proliferation, migration, secretion of bioactive molecules and turnover of the extracellular matrix. Many of the key cellular responses of the heart to injury or stress are mediated via specific signaling cascades involving the stress-activated protein kinases (SAPKs). The SAPKs comprise the p38 MAPK and c-Jun N-terminal kinase families, both of which have been implicated in promoting myocardial damage and adverse cardiac remodeling. This article focuses on SAPK signaling cascades in the heart, with particular emphasis on their modulatory effects on cardiac fibroblast function, inflammation and fibrosis. It also describes current and future therapeutic strategies for inhibiting SAPKs in the myocardium. Understanding the role of SAPK signaling at the cellular level holds potential for developing novel therapies to ameliorate cardiac dysfunction in man.
authors.affiliation: Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health & Therapeutics (LIGHT) & Multidisciplinary Cardiovascular Research Centre (MCRC), University of Leeds, Leeds, UK. n.a.turner@leeds.ac.uk
authors.forename: Neil A
authors.initials: NA
authors.lastname: Turner
mesh_terms: D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D005355:Fibrosis; D006321:Heart / Q000502:physiology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000502:physiology; D020930:MAP Kinase Kinase Kinases / Q000502:physiology; D048290:Mitogen-Activated Protein Kinase 11 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000502:physiology*; D009206:Myocardium / Q000166:cytology* / Q000473:pathology; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D007093:Imidazoles; D011725:Pyridines; D048290:Mitogen-Activated Protein Kinase 11; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; D048670:MAP Kinase Kinase 4; C093642:SB 203580