Kinase inhibitors for cardiovascular disease |
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Authors: | Kumar Rajesh Singh Vivek P Baker Kenneth M |
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Affiliation: | Division of Molecular Cardiology, Cardiovascular Research Institute, Texas A&M University System Health Science Center, College of Medicine, Temple, TX 76504, USA. |
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Abstract: | Over the last decade, there has been substantial progress toward understanding the pathophysiology and treatment of cardiovascular diseases (CVDs). Elucidating cellular responses to the extracellular environment and signal transduction mechanisms have provided the opportunity to explore novel molecular therapeutic approaches for the treatment of CVDs. Neurohormonal stimulation has been implicated in these diseases; blockade of the renin-angiotensin and beta-adrenergic systems are examples of therapeutic effectiveness. There are multiple cell signaling cascades, some of which are beneficial or compensatory and others deleterious. The balance between these pathways, which in large part is dictated by the cellular environment, determines the outcome as a diseased or non-diseased state. Selective targeting of signaling pathways using protein kinase inhibitors, would have a potential advantage over receptor blockers. We review potential protein kinase targets and recent evidence supporting therapeutic interventional value in CVDs. |
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Keywords: | β-ARs, β-adrenergic receptors AM, adrenomedullin Ang II, angiotensin II CaMKII, Ca2+/calmodulin-dependent protein kinase II CVDs, cardiovascular diseases CHF, congestive heart failure CAD, coronary artery disease ET-1, endothelin-1 eNOS, endothelial nitric oxide synthase EPCs, endothelial progenitor cells βARKct, Gβγ sequestering peptide of β-ARK1 GSK, glycogen synthase kinase GPCRs, G-protein-coupled receptors GRKs, G-protein-coupled receptor kinases IRS-1, insulin receptor substrate-1 mTOR, mammalian target of rapamycin MAPKs, mitogen-activated protein kinases MLCP, myosin light chain phosphatase NKCC, Na,K,2Cl-cotransporter L-NAME, Nw-nitro- smallcaps" >l-arginine methyl ester PI-3K, phosphoinositide-3 kinase PKC, protein kinase C ROS, reactive oxygen species ROCK, Rho-dependent kinase RAS, renin-angiotensin system TGFβ, transforming growth factor-β TF, tissue factor VEGF, vascular endothelial growth factor VSMC, vascular smooth muscle cell |
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