Kinase inhibitors for cardiovascular disease.
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.
Kumar
Rajesh
R
Division of Molecular Cardiology, Cardiovascular Research Institute, Texas A&M University System Health Science Center, College of Medicine, Temple, TX 76504, USA.
Singh
Vivek P
VP
Baker
Kenneth M
KM
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D020935:MAP Kinase Signaling System; D008955:Models, Cardiovascular; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D058570:TOR Serine-Threonine Kinases; D020741:rho GTP-Binding Proteins; C546842:MTOR protein, human