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

对于哺乳动物物种来说，在特定的生态位中生存需要与当地需求（例如，身体活动和体温调节需求）相匹配的衍生心血管（CV）表型。相反，个体的生存可能取决于对当地环境急剧变化的表型可塑性。尽管在人类中对体力活动变化引起的心血管重塑进行了广泛的研究，但物种特异性体力活动模式对衍生的心血管系统的影响尚未在人类或其他哺乳动物中得到仔细研究。最近，使用比较方法，我和我的学员们已经证明，与黑猩猩相比，人类的心脏表型可能被选择为定期的耐力活动。这一进化史可能有助于解释后工业化人类生活在进化上不合适的生活方式中的CV适应不良。

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 inor outside oftheir 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.