左右心室衰老的分子和生理机制各不相同

IF 8 1区 医学 Q1 CELL BIOLOGY
Aging Cell Pub Date : 2024-09-19 DOI:10.1111/acel.14339
Benjamin D. McNair, Aykhan Yusifov, Joshua P. Thornburg, Caleb R. Hoopes, Sushumna B. Satyanarayana, Tathagato Roy, Jason P. Gigley, Danielle R. Bruns
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引用次数: 0

摘要

衰老是心脏病的主要风险因素,而心脏病是导致全球死亡的主要原因。右心室(RV)功能可预测几种与年龄相关的临床情况下的存活率,但目前还没有直接改善右心室功能的疗法,这在很大程度上是由于人们对右心室衰老的机理及其与被广泛研究的左心室(LV)的不同之处了解甚少。为了弥补这一不足,我们全面量化了随年龄增长的 RV 功能和形态重塑。我们进一步旨在确定 RV 衰老的分子机制,因此我们对雌雄幼年(4 个月)和老年(19-21 个月)C57BL6 小鼠的 RV 和 LV 进行了 RNA 序列分析。与左心室发生的同心性肥厚重塑和舒张功能障碍相反,衰老的 RV 发生了偏心性重塑,并伴有明显的扩张和收缩功能受损。转录组数据也与心室特异性衰老一致,衰老心室之间共享的基因很少(13%)。KEGG 分析发现了炎症和免疫细胞通路中的共享衰老基因,流式细胞术证实了这一点,并显示两个心室中 GR1+ 髓样细胞的比例都较高。独特的 RV 老化基因富含饱和脂肪酸的生物合成、PPAR 信号转导和丁酸盐代谢,我们还发现了推测的新的 RV 特异性老化基因。总之,我们认为 RV 和 LV 是独特的心腔,随着年龄的增长会发生不同的重塑。这些强大的差异可能解释了为什么基于左心室研究设计的疗法不能改善左心室功能,并表明未来强调心室差异的努力可能会阐明健康心脏衰老的新疗法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Molecular and physiological mechanisms of aging are distinct in the cardiac right and left ventricles

Molecular and physiological mechanisms of aging are distinct in the cardiac right and left ventricles
Aging is the primary risk factor for heart disease, the leading global cause of death. Right ventricular (RV) function predicts survival in several age-related clinical contexts, yet no therapies directly improve RV function, in large part due to a poor mechanistic understanding of RV aging and how it is distinct from the widely studied left ventricle (LV). To address this gap, we comprehensively quantified RV functional and morphological remodeling with age. We further aimed to identify molecular mechanisms of RV aging thus we performed RNAseq on RV and LV from male and female young (4 months) and aged (19–21 months) C57BL6 mice. Contrary to the concentric hypertrophic remodeling and diastolic dysfunction that occurs in the LV, the aging RV underwent eccentric remodeling with significant dilation and impaired systolic function. Transcriptomic data were also consistent with ventricle-specific aging, with few genes (13%) similarly shared between ventricles with aging. KEGG analysis identified shared aging genes in inflammatory and immune cell pathways that were confirmed by flow cytometry that demonstrated higher percent of GR1+ myeloid cells in both ventricles. Unique RV aging genes enriched in the biosynthesis of saturated fatty acids, PPAR signaling, and butanoate metabolism, and we identified putative novel RV-specific aging genes. Together, we suggest that the RV and LV are unique cardiac chambers that undergo distinct remodeling with age. These robust differences may explain why therapies designed from LV-based studies fail to improve RV function and suggest that future efforts emphasizing ventricular differences may elucidate new therapies for healthy cardiac aging.
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来源期刊
Aging Cell
Aging Cell Biochemistry, Genetics and Molecular Biology-Cell Biology
自引率
2.60%
发文量
212
期刊介绍: Aging Cell is an Open Access journal that focuses on the core aspects of the biology of aging, encompassing the entire spectrum of geroscience. The journal's content is dedicated to publishing research that uncovers the mechanisms behind the aging process and explores the connections between aging and various age-related diseases. This journal aims to provide a comprehensive understanding of the biological underpinnings of aging and its implications for human health. The journal is widely recognized and its content is abstracted and indexed by numerous databases and services, which facilitates its accessibility and impact in the scientific community. These include: Academic Search (EBSCO Publishing) Academic Search Alumni Edition (EBSCO Publishing) Academic Search Premier (EBSCO Publishing) Biological Science Database (ProQuest) CAS: Chemical Abstracts Service (ACS) Embase (Elsevier) InfoTrac (GALE Cengage) Ingenta Select ISI Alerting Services Journal Citation Reports/Science Edition (Clarivate Analytics) MEDLINE/PubMed (NLM) Natural Science Collection (ProQuest) PubMed Dietary Supplement Subset (NLM) Science Citation Index Expanded (Clarivate Analytics) SciTech Premium Collection (ProQuest) Web of Science (Clarivate Analytics) Being indexed in these databases ensures that the research published in Aging Cell is discoverable by researchers, clinicians, and other professionals interested in the field of aging and its associated health issues. This broad coverage helps to disseminate the journal's findings and contributes to the advancement of knowledge in geroscience.
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