Protein kinase cascades in the regulation of cardiac hypertrophy.
In broad terms, there are 3 types of cardiac hypertrophy: normal growth, growth induced by physical conditioning (i.e., physiologic hypertrophy), and growth induced by pathologic stimuli. Recent evidence suggests that normal and exercise-induced cardiac growth are regulated in large part by the growth hormone/IGF axis via signaling through the PI3K/Akt pathway. In contrast, pathological or reactive cardiac growth is triggered by autocrine and paracrine neurohormonal factors released during biomechanical stress that signal through the Gq/phospholipase C pathway, leading to an increase in cytosolic calcium and activation of PKC. Here we review recent developments in the area of these cardiotrophic kinases, highlighting the utility of animal models that are helping to identify molecular targets in the human condition.
Dorn
Gerald W
GW
Heart and Vascular Center, Medical Center, University of Cincinnati, Cincinnati, Ohio 45267-0542, USA. dorngw@ucmail.uc.edu
Force
Thomas
T
D000818:Animals; D006332:Cardiomegaly / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D038341:Glycogen Synthase Kinases / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000502:physiology*
D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D038341:Glycogen Synthase Kinases; D007527:Isoenzymes; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494918:AKT1 protein, human