Abnormalities of calcium metabolism and myocardial contractility depression in the failing heart.
Heart failure (HF) is characterized by molecular and cellular defects which jointly contribute to decreased cardiac pump function. During the development of the initial cardiac damage which leads to HF, adaptive responses activate physiological countermeasures to overcome depressed cardiac function and to maintain blood supply to vital organs in demand of nutrients. However, during the chronic course of most HF syndromes, these compensatory mechanisms are sustained beyond months and contribute to progressive maladaptive remodeling of the heart which is associated with a worse outcome. Of pathophysiological significance are mechanisms which directly control cardiac contractile function including ion- and receptor-mediated intracellular signaling pathways. Importantly, signaling cascades of stress adaptation such as intracellular calcium (Ca(2+)) and 3'-5'-cyclic adenosine monophosphate (cAMP) become dysregulated in HF directly contributing to adverse cardiac remodeling and depression of systolic and diastolic function. Here, we provide an update about Ca(2+) and cAMP dependent signaling changes in HF, how these changes affect cardiac function, and novel therapeutic strategies which directly address the signaling defects.
Lehnart
Stephan E
SE
Department of Cardiology & Pulmonology, Center of Molecular Cardiology, UMG Heart Center, Georg August University Medical School, Goettingen, Germany. slehnart@med.uni-goettingen.de
Maier
Lars S
LS
Hasenfuss
Gerd
G
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D012964:Sodium / Q000378:metabolism
D019837:Ryanodine Receptor Calcium Release Channel; D012964:Sodium; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D002118:Calcium