Potential of p38-MAPK inhibitors in the treatment of ischaemic heart disease.
Chronic heart failure is debilitating, often fatal, expensive to treat and common. In most patients it is a late consequence of myocardial infarction (MI). The intracellular signals following infarction that lead to diminished contractility, apoptosis, fibrosis and ultimately heart failure are not fully understood but probably involve p38-mitogen activated protein kinases (p38), a family of serine/threonine kinases which, when activated, cause cardiomyocyte contractile dysfunction and death. Pharmacological inhibitors of p38 suppress inflammation and are undergoing clinical trials in rheumatoid arthritis, Chrohn's disease, psoriasis and surgery-induced tissue injury. In this review, we discuss the mechanisms, circumstances and consequences of p38 activation in the heart. The purpose is to evaluate p38 inhibition as a potential therapy for ischaemic heart disease.
Clark
James E
JE
The Cardiovascular Division, King's College London, The Rayne Institute, St Thomas' Hospital, London, SE1 7EH, United Kingdom.
Sarafraz
Negin
N
Marber
Michael S
MS
D000818:Animals; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases