A Multi-Target Pharmacological Correction of a Lipoyltransferase LIPT1 Gene Mutation in Patient-Derived Cellular Models

Abstract

Simple Summary Cardiovascular diseases represent the leading cause of mortality and morbidity worldwide, and age is an important contributing factor. Preclinical models are crucial for exploring and understanding the physiology of the heart and age-related changes, as well as cardiac pathological aspects. In line with this, the Octodon degus (O. degus) is a diurnal rodent that has been claimed as an interesting model for aging research. However, several aspects of this experimental model are not fully characterized yet. In this work, we evaluated the cardiac electric activity by electrocardiogram recording in the aging process, considering differences between males and females. We provide the normal ranges for the heart rate, duration and voltage of the ECG waves and intervals, as well as electrical axis deviation. Our results demonstrate that both age and sex influence the cardiac function and the incidence of arrhythmias. Therefore, this research indicates that this rodent model could be useful for cardiovascular research, including impacts of aging and biological sex.Cardiovascular diseases represent the leading cause of mortality and morbidity worldwide, and age is an important risk factor. Preclinical models provide supportive evidence toward age-related cardiac changes, as well as allow for the study of pathological aspects of the disease. In the present work, we evaluated the electrocardiogram (ECG) recording in the O. degus during the aging process in both females and males. Taking into account the age and sex, our study provides the normal ranges for the heart rate, duration and voltage of the ECG waves and intervals, as well as electrical axis deviation. We found that the QRS complex duration and QTc significantly increased with age, whereas the heart rate significantly decreased. On the other hand, the P wave, PR and QTc segments durations, S wave voltage and electrical axis were found to be significantly different between males and females. The heart rhythm was also altered in aged animals, resulting in an increased incidence of arrhythmias, especially in males. Based on these results, we suggest that this rodent model could be useful for cardiovascular research, including impacts of aging and biological sex.