Mammalian cardiac structure and function: The influence of evolutionary selection and prevailing hemodynamics

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For mammalian species, survival within a specific ecological niche requires a derived cardiovascular (CV) phenotype matched to the local demands (e.g., physical activity and thermoregulatory requirements). In contrast, survival of the individual likely depends on phenotypic plasticity to acute changes in the local environment. Although CV remodeling in response to changes in physical activity has been widely studied in humans, the influence of species-specific physical activity patterns on the derived CV system has not been closely examined in humans or other mammals. Recently, using the comparative approach, my trainees and I have shown that in comparison to the chimpanzee the human cardiac phenotype may have been selected for regular endurance activity. This evolutionary history may help explain CV maladaptation in post-industrialized humans living evolutionarily-inappropriate lifestyles. The long-term objectives of my research program are to better understand how evolution and phenotypic plasticity shape the mammalian CV system and to explore mechanisms that underpin CV mismatch and maladaptation in mammals living outside of their evolutionary niche. My short-term objectives are to: 1. Determine the influence of natural selection on the human vascular phenotype; 2. Uncover the influence of natural and artificial selection on the derived mammalian heart; 3. Characterize functional remodeling in the human heart; and 4. Establish the mechanisms underpinning CV maladaptation in post-industrialized humans. I have established a multi-disciplinary, multi-national, program of research predicated on an extensive network of collaborators that includes world-leading experts in evolutionary science, veterinary science, and CV physiology as well as established relationships with a number of wildlife sanctuaries and zoological collections across the world. This program of research will result in a better understanding of the role of natural, or artificial, selection on the derived mammalian CV system and will improve our understanding of phenotypic remodeling to changes in hemodynamic load. Furthermore, findings from my work will shed light on the regulation, or dysregulation, of CV structure and function in species living in-or outside of-their evolutionary niche. These studies and the data collected will have far-reaching implications for collaborative efforts with human and animal clinicians examining the causes and consequences of, and interventions for, CV health and disease. Importantly, the diverse combination of approaches and techniques proposed, alongside the involvement of my diverse network of subject-expert collaborators, will also provide my trainees with an incredibly rich research environment.