Myofilament dysfunction as an emerging mechanism of volume overload heart failure.
Two main hemodynamic overload mechanisms [i.e., volume and pressure overload (VO and PO, respectively] result in heart failure (HF), and these two mechanisms have divergent pathologic alterations and different pathophysiological mechanisms. Extensive evidence from animal models and human studies of PO demonstrate a clear association with alterations in Ca(2+) homeostasis. By contrast, emerging evidence from animal models and patients with regurgitant valve disease and dilated cardiomyopathy point toward a more prominent role of myofilament dysfunction. With respect to VO HF, key features of excitation-contraction coupling defects, myofilament dysfunction, and extracellular matrix composition will be discussed.
Center for Cardiovascular and Pulmonary Research and The Heart Center, Nationwide Children's Hospital, Columbus, OH, USA.
Kristin
K
Wilson
Pamela A
PA
Lucchesi
D000818:Animals; D056966:Excitation Contraction Coupling; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D009210:Myofibrils / Q000378:metabolism* / Q000502:physiology