Abstract
Our understanding of how aging affects the cellular and molecular components of the vasculature and contributes to cardiovascular diseases is still limited. Here we report a single-cell transcriptomic survey of aortas and coronary arteries in young and old cynomolgus monkeys. Our data define the molecular signatures of specialized arteries and identify eight markers discriminating aortic and coronary vasculatures. Gene network analyses characterize transcriptional landmarks that regulate vascular senility and position FOXO3A, a longevity-associated transcription factor, as a master regulator gene that is downregulated in six subtypes of monkey vascular cells during aging. Targeted inactivation of FOXO3A in human vascular endothelial cells recapitulates the major phenotypic defects observed in aged monkey arteries, verifying FOXO3A loss as a key driver for arterial endothelial aging. Our study provides a critical resource for understanding the principles underlying primate arterial aging and contributes important clues to future treatment of age-associated vascular disorders.
Highlights
Our understanding of how aging affects the cellular and molecular components of the vasculature and contributes to cardiovascular diseases is still limited
Targeted inactivation of Forkhead box O3A (FOXO3A) in human arterial vascular endothelial cells (ECs), which results in the disruption of cellular homeostasis, recapitulates the major phenotypic defects observed in aged monkey arteries
To study the subpopulation structure and molecular characteristics of the aged monkey vasculature, we performed single-cell RNA sequencing on lesionprone aortas and coronary arteries sampled from eight young and eight old cynomolgus monkeys (Fig. 1a, Supplementary Fig. 1a, and Supplementary Data 1)
Summary
Our understanding of how aging affects the cellular and molecular components of the vasculature and contributes to cardiovascular diseases is still limited. We report a single-cell transcriptomic survey of aortas and coronary arteries in young and old cynomolgus monkeys. We obtain single-cell transcriptomic atlas of the atherosclerosis-prone aortic arch and coronary artery in young and aged nonhuman primates, cynomolgus monkeys. Based on this dataset, we identify unique molecular signatures illustrating aorta- and coronary artery-specific cell diversity. Targeted inactivation of FOXO3A in human arterial vascular endothelial cells (ECs), which results in the disruption of cellular homeostasis, recapitulates the major phenotypic defects observed in aged monkey arteries. Our work provides a comprehensive understanding of aortic and coronary vasculature aging at single-cell level, which paves the way for new therapies against human cardiovascular diseases
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