Sarcomeres and the Biophysics of Heart Failure

Article Commentary: Prospects for In Vitro Myofilament Maturation in Stem Cell-Derived Cardiac Myocytes

“…The MHC isoforms are known to have different ATPase activities, actin sliding velocities, and power output. 80 More specifically, α-MHC, the faster of the two, has several-fold higher myofibrillar actomyosin-activated ATPase activity. This means that this isoform sacrifices economy of tension for the ability to contract at greater speed.…”

“…78 In heart failure, the expression decreases to 50%–55%. 78–80 Nonfailing adult human ventricular myocardium expresses mainly β-MHC with a low (0%–15%) but detectable α-MHC content. 81,82 Reiser et al found that fetal ventricular tissue at gestational week 12 already expressed the adult level of α-MHC.…”

“…78 The amount of α-MHC in samples from patients with heart failure or hypertrophy was reduced further to 0%–4%. 75,78,80,83,84 These small shifts can have a profound influence on contractile function, underscoring their role in cardiac development and the cardiac response to different hemodynamic perturbations. 85–87…”

“…10,11,15,55,56,94 With their cardiac patch, Zhang et al 10 achieved a β-MHC/α-MHC ratio of about 3:5 in comparison to an approximate ratio of 9:1 in adult human tissue. 80–82 Their construct hence expresses predominantly the fast MHC isoform. Turnbull et al express an even lower β-MHC:α-MHC ratio, which might explain why their twitch kinetics are faster than observed in adult human tissue.…”