Intracellular MAPK (mitogen-activated protein kinase) signalling cascades probably play an important role in the pathogenesis of cardiac and vascular disease. A substantial amount of basic science research has defined many of the details of MAPK pathway organization and activation, but the role of individual signalling proteins in the pathogenesis of various cardiovascular diseases is still being elucidated. In the present review, the role of the MAPKs ERK (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase) and p38 MAPK in cardiac hypertrophy, cardiac remodelling after myocardial infarction, atherosclerosis and vascular restenosis will be examined, with attention paid to genetically modified murine model systems and to the use of pharmacological inhibitors of protein kinases. Despite the complexities of this field of research, attractive targets for pharmacological therapy are emerging.
- intracellular signalling
- mitogen-activated protein kinase (MAPK)
- myocardial infarction
Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ANF, atrial natriuretic factor; apoE, apolipoprotein E; ASK1, apoptosis signal-regulating kinase 1; ATM, ataxia telangectasia mutated; CKO, cardiac-specific knockout; DN, dominant-negative; DUSP6, dual-specificity phosphatase 6; eIF4E, eukaryotic initiation factor 4E; ERK, extracellular-signal-regulated kinase; ET1, endothelin 1; FGF1, fibroblast growth factor 1; GPCR, G-protein-coupled receptor; Grb2, growth-factor-receptor-bound protein 2; JNK, c-Jun N-terminal kinase; LAD, left anterior descending; LDL, low-density lipoprotein; acLDL, acetylated LDL; L-NAME, NG-nitro-L-arginine methyl ester; LV, left ventricular; MAPK, mitogen-activated protein kinase; MEK, MAPK/ERK kinase; MEKK, MEK kinase; MHC, myosin heavy chain; MI, myocardial infarction; MKK, MAPK kinase; MKKK, MAPK kinase kinase; MLC, myosin light-chain; Mnk, MAPK-interacting kinase; mTOR, mammalian target of rapamycin; NFAT, nuclear factor of activated T-cells; oxLDL, oxidized LDL; p90RSK, 90 kDa ribosomal protein S6 kinase; PDGF, platelet-derived growth factor; PI3Kα, phosphoinositide 3-kinase α; Rb, retinoblastoma protein; ROS, reactive oxygen species; RTK, receptor tyrosine kinase; SH2, Src homology 2; SMC, smooth muscle cell; SOS, Son of sevenless; SR-A, scavenger receptor A; TAC, transverse aortic constriction; TAK1, transforming growth factor-β-activated kinase 1; VSMC, vascular SMC
- © The Authors Journal compilation © 2008 Biochemical Society