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Kinase inhibitors for cardiovascular disease
Authors:Kumar Rajesh  Singh Vivek P  Baker Kenneth M
Affiliation:Division of Molecular Cardiology, Cardiovascular Research Institute, Texas A&M University System Health Science Center, College of Medicine, Temple, TX 76504, USA.
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.
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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