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.

Tnni3k alleles influence ventricular mononuclear diploid cardiomyocyte frequency

“…Prior studies have reported H . glaber heart morphology and physiology [34, 35], although CM polyploidy had not been addressed. We conducted an analysis of ventricular CM composition in juvenile-adult stage naked mole-rats, using the same procedures as used for mouse heart analysis.…”

A comparison of the mitochondrial proteome and lipidome in the mouse and long-lived Pipistrelle bats

“…However, two of the proteins significantly altered between the mouse and bat skeletal muscle are best known for their distribution in cardiac muscle, namely myosin light chain 2 and fatty acid binding protein 3 (FABP3) [31,32]. Myosin light chain 2 has been found to have half the levels of phosphorylation in the naked mole rat when compared with the mouse, which makes this an especially interesting protein in exceptionally long-lived species [33]. We have now confirmed that FABP3 is much more abundant in the bat muscle mitochondria.…”

Cardiac metabolomic profile of the naked mole-rat—glycogen to the rescue

“…High resolution 1 H MRS based metabolomic analysis of NMR heart tissue (representative spectra shown in figure 1) revealed distinctly different metabolomic profiles compared to C57/BL6 hearts (figure 2 b ) and changes in several key metabolites were observed (figure 2 c , d ). Despite reduced contractile performance and baseline hypertrophy [12–15], NMR hearts were not energetically compromised as the levels of creatine and ATP were comparable to C57/BL6 wild-type hearts. Myocardial glycogen and glucose-1-phosphate levels (G-1-P) resulting from glycogen turnover were significantly higher in the NMR hearts and were undetectable in C57/BL6 mouse hearts ( p < 0.001; figure 2 e ).…”