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

Autor: McNair BD; Kinesiology and Health, University of Wyoming, Laramie, Wyoming, USA., Yusifov A; Kinesiology and Health, University of Wyoming, Laramie, Wyoming, USA., Thornburg JP; Kinesiology and Health, University of Wyoming, Laramie, Wyoming, USA., Hoopes CR; WWAMI Medical Education, University of Washington School of Medicine, Seattle, Washington, USA., Satyanarayana SB; Kinesiology and Health, University of Wyoming, Laramie, Wyoming, USA., Roy T; Molecular Biology, University of Wyoming, Laramie, Wyoming, USA., Gigley JP; Molecular Biology, University of Wyoming, Laramie, Wyoming, USA., Bruns DR; Kinesiology and Health, University of Wyoming, Laramie, Wyoming, USA.; WWAMI Medical Education, University of Washington School of Medicine, Seattle, Washington, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2024 Sep 19, pp. e14339. Date of Electronic Publication: 2024 Sep 19.
DOI: 10.1111/acel.14339
Abstrakt: 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.
(© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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