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

哺乳动物心脏结构和功能：进化选择和流行血流动力学的影响

• 批准号: RGPIN-2020-04637
• 负责人: Shave, Rob
• 金额: $ 2.91万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=716583
• 关键词: Mammalian; cardiac; structure; function; influence

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.

对于哺乳动物物种，在特定生态位内的生存需要与当地需求相匹配的衍生心血管（CV）表型（例如，身体活动和体温调节要求）。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。虽然CV重塑响应于身体活动的变化已被广泛研究，在人类中，物种特异性的身体活动模式对衍生的CV系统的影响尚未在人类或其他哺乳动物中仔细检查。最近，我和我的学员通过比较研究发现，与黑猩猩相比，人类的心脏表型可能更适合进行有规律的耐力活动。这种进化史可能有助于解释后工业化人类生活在进化上不适当的生活方式中的CV适应不良。 我的研究计划的长期目标是更好地了解进化和表型可塑性如何塑造哺乳动物CV系统，并探索机制，支持CV不匹配和适应不良的哺乳动物生活在他们的进化生态位之外。我的短期目标是： 1.确定自然选择对人类血管表型的影响; 2.揭示自然和人工选择对衍生哺乳动物心脏的影响; 3.表征人类心脏的功能重塑;以及 4.建立后工业化人类CV适应不良的基础机制。 我已经建立了一个多学科，多国家的研究计划，该计划基于广泛的合作者网络，其中包括进化科学，兽医科学和CV生理学方面的世界领先专家，以及与世界各地的一些野生动物保护区和动物学收藏建立了关系。这项研究计划将导致更好地了解自然或人工选择对衍生哺乳动物CV系统的作用，并将提高我们对血液动力学负荷变化的表型重塑的理解。此外，我的研究结果将阐明生活在其进化生态位内或外的物种中CV结构和功能的调节或失调。这些研究和收集的数据将对与人类和动物临床医生的合作产生深远的影响，这些临床医生将检查CV健康和疾病的原因和后果以及干预措施。重要的是，所提出的方法和技术的多样化组合，以及我的学科专家合作者的多样化网络的参与，也将为我的学员提供一个令人难以置信的丰富的研究环境。