Why the study?
Mouse lemurs replicate human senescence processes and could serve as a model for cardiovascular dysfunctions, but their cardiac physiology was unknown.
The gray mouse lemur represents a novel nonhuman primate model for studying cardiac pacemaker activity and age-related heart rate dysfunctions, bridging the gap between small rodents and humans.
Provides first cardiac data in this primate model; leaves open translation to human cardiovascular aging.
Background Gray mouse lemurs ( Microcebus murinus ) are the smallest and most ancestral primates known. Their size falls in between that of mice and rats, and their genetic proximity to humans makes them an emerging model to study age-related neurodegeneration. Since mouse lemurs replicate similar senescence processes of humans, they constitute a useful model for studying cardiovascular dysfunctions. However, their cardiac physiology is unknown. Thus, we investigated the cardiac pacemaker activity generated by the sinoatrial node (SAN) of mouse lemurs, presenting the first characterization of heart automaticity in nonhuman primates. Methods and Results We recorded cardiac automaticity in mouse lemurs and in their SAN tissues and pacemaker myocytes. Mouse lemurs have a heart rate (HR) in between those of mice and rats and a similar generation of the SAN electrical impulse. Their SAN myocytes express the main pacemaker currents at densities similar to mice: the hyperpolarization-activated current ( I f ) and the L-type ( I ca,L ) and T-type ( I ca,T ) calcium currents. Conversely, their ventricular depolarization resembles that of large mammals and despite the small size of mouse lemurs, the total number of heartbeats in their life corresponds to what can be attained by humans. Using muscle-derived stem cells (MDSCs) from mouse lemurs, we also differentiated pacemaker-like (PML) cells showing spontaneous automaticity and expressing markers of native SAN myocytes (HCN4 and connexin-45). Conclusions Our characterization of heart automaticity in Microcebus murinus provides new opportunities for comparative cardio-physiology studies in primates and with humans and for testing molecules that could modulate age-related dysfunctions of heart rate.
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DiFrancesco et al. (2021) studied this question.
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