The p38 mitogen-activated protein kinase pathway--a potential target for intervention in infarction, hypertrophy, and heart failure.
The p38 mitogen-activated protein kinases (p38s) are stress-activated Ser/Thr kinases. Their activation has been associated with various pathological stressors in the heart. Activated p38 is implicated in a wide spectrum of cardiac pathologies, including hypertrophy, myocardial infarction, as well as systolic and diastolic heart failure. In this review, the specific contribution of different isoforms of p38 kinases to cardiac diseases as well as TAB-1-mediated non-canonical activation pathway are discussed as a rationale for inhibiting p38 activity to treat cardiac hypertrophy, ischemic injury, and heart failure. Finally, a summary of current clinical trials targeting p38 kinases in cardiovascular diseases is provided to highlight the potential promise as well as existing challenges of this therapeutic approach. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."
King's College London BHF Centre, Cardiovascular Division, The Rayne Institute, St. Thomas' Hospital, London SE1 7EH, United Kingdom. mike.marber@kcl.ac.uk
Michael S
MS
Marber
Beth
B
Rose
Yibin
Y
Wang
D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D058990:Molecular Targeted Therapy; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D007527:Isoenzymes; D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases