Background—Chronic congestive heart failure is a common, often lethal disorder of cardiac contractility. The fundamental pathophysiology of thecontractilefailure remains unclear, the focus being on abnormal Ca2+ cycling despite emerging evidence for depressed myofilament function. Methods and Results—We measured intracellular Ca2+ concentration ([Ca2+]i) andcontractileforce in intact ...
Here we focus on diastolicdysfunctionin cardiomyopathies, which is caused bycontractileprotein mutations and malfunction in myocardial cells. In myofibrils, myosin is a motor protein that causes crossbridge formation when myosin attaches to thin filament actin.
A number of subcellular alterations to the cardiomyocyte contribute tocontractiledysfunctionin early DCM. While changes in Ca 2+ handling protein expressions are evident and likely contribute to the prolongation of systole and relaxation, diminished intracellular Ca 2+ transients appear to be associated only with advanced DCM.
Few studies have examined whether chronic posttranslational modifications within the myofilament contribute tocontractiledysfunction. Earlier work indicates increased PKC expression and activity are linked to human HF (Bowling et al., 1999; Noguchi et al., 2004), but the role played by its downstream myofilament targets indysfunctionis not clear. The present study shows PKC-targeted human ...
The pathologic stimuli for the occurrence of heart failure can be categorized as follows: (a) conditions which lead to the development of pressure or volume overload (b) conditions which produce abnormal cardiac muscle contraction and relaxation and (c) conditions which limit ventricular filling. 2 A wide variety of diseases (Table I) including ...
