The naked mole-rat exhibits an unusual cardiac myofilament protein profile providing new insights into heart function of this naturally subterranean rodent

Abstract

The long-lived, hypoxic-tolerant naked mole-rat well-maintains cardiac function over its three-decade-long lifespan and exhibits many cardiac features atypical of similar-sized laboratory rodents. For example, they exhibit low heart rates and resting cardiac contractility, yet have a large cardiac reserve. These traits are considered ecophysiological adaptations to their dank subterranean atmosphere of low oxygen and high carbon dioxide levels and may also contribute to negligible declines in cardiac function during aging. We asked if naked mole-rats had a different myofilament protein signature to that of similar-sized mice that commonly show both high heart rates and high basal cardiac contractility. Adult mouse ventricles predominantly expressed α-myosin heavy chain (97.9 ± 0.4%). In contrast, and more in keeping with humans, β myosin heavy chain was the dominant isoform (79.0 ± 2.0%) in naked mole-rat ventricles. Naked mole-rat ventricles diverged from those of both humans and mice, as they expressed both cardiac and slow skeletal isoforms of troponin I. This myofilament protein profile is more commonly observed in mice in utero and during cardiomyopathies. There were no species differences in phosphorylation of cardiac myosin binding protein-C or troponin I. Phosphorylation of both ventricular myosin light chain 2 and cardiac troponin T in naked mole-rats was approximately half that observed in mice. Myofilament function was also compared between the two species using permeabilized cardiomyocytes. Together, these data suggest a cardiac myofilament protein signature that may contribute to the naked mole-rat’s suite of adaptations to its natural subterranean habitat.

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Acknowledgements

This work was supported in part by the following grants: American Heart Association, 12GRNT12030299 and 15GRNT22420022 (R. Buffenstein); National Institutes of Health Training Grant, T32 AG021890 (K.M. Grimes); National Institutes of Health, R01 HL105826 and K02 HL114749 (S. Sadayappan) and the American Heart Association Grant-in-Aid, 14GRNT20490025 (S. Sadayappan); National Institutes of Health, P01 HL62426 and R01 HL75494 (P.P. de Tombe); American Heart Association Midwest Predoctoral Fellowship, 11PRE7240022 (D.Y. Barefield); and National Institutes of Health shared instrumentation grant S10RR025111 (S.T. Weintraub). Mass spectrometry analyses were conducted in the University of Texas Health Science Center at San Antonio Institutional Mass Spectrometry Laboratory; the expert technical assistance of Sammy Pardo is gratefully acknowledged.

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Grimes, K.M., Barefield, D.Y., Kumar, M. et al. The naked mole-rat exhibits an unusual cardiac myofilament protein profile providing new insights into heart function of this naturally subterranean rodent. Pflugers Arch - Eur J Physiol 469, 1603–1613 (2017). https://doi.org/10.1007/s00424-017-2046-3

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Keywords

  • Naked mole-rat
  • Heart
  • Slow skeletal troponin I
  • β myosin heavy chain
  • Neoteny
  • Hypoxia