Abstract 19086: Myofilament Proteins of the Naked Mole-rat Heart Reflect Low Basal Species Cardiac Function

Abstract

The naked mole-rat (NMR) is a mouse-sized rodent with a maximum longevity of >31 years. The species exhibits low basal heart rate (256 bpm) and cardiac output (7 ml/min) for its body size, as well as low fractional shortening (28%) for a rodent. However unlike other well-studied mammals, the NMR maintains cardiac reserve and diastolic function for at least 75% of its maximum lifespan - at ages equivalent to 90 year old humans. We questioned if this low basal cardiac function was due to NMR myofilament composition and function. NMR ventricles are comprised primarily of the β-myosin heavy chain isoform, which is associated with slowed myocardial contraction and increased efficiency. This is in stark contrast to mouse ventricles, which express predominately the α-isoform, and switch to the β-isoform upon experimental induction of heart failure. Compared to mice, NMR myofilament proteins such as cardiac troponin I and cardiac myosin binding protein-C display lower levels of phosphorylation. Such levels are indicative of decreased activation of myofilament proteins and may relate to the species’ low basal cardiac function. Both the NMR’s predominance of β-myosin heavy chain and the low basal level of myofilament phosphorylation present a phenotype much closer to that seen in human ventricles than in those of mice. Intriguingly, maximal force developed by skinned NMR cardiomyocytes is not significantly different to that of mouse cardiomyocytes (NMR: 70.9 ± 9.3mN/mm2 vs. mouse: 87.7 ± 0.6 mN/mm2). This is likely a reflection of the NMR’s ability to enhance cardiac function to the level of a mouse when stimulated, as is evident when both species are treated in vivo with dobutamine (3 μg/g i.p.). Such low basal cardiac function may put less overall strain on the heart over time and could be critical to the NMR’s ability to maintain cardiac function with age.