Single cell mapping of large and small arteries during hypertensive aging

Vascular aging is directly related to several major diseases including hypertension and atherosclerosis, in which endothelial dysfunction and smooth muscle phenotype changes are crucial. However, cell types within the vessel wall and their dynamic cellular communication status have not been characterized in different arteries during hypertensive aging. To depict the interconnectedness of complex mechanism between hypertension and aging, we performed single cell RNA sequencing of aorta, femoral and mesentery artery, respectively from Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) aging 16-72 weeks. We found that aging and hypertension alone have a significant impact on the alteration of cellular composition and artery remodeling both on conductive and resistant arteries, even greater when superimposed. Consistently, smooth muscle cells (SMCs) underwent phenotypic switching from contractile towards synthetic, apoptotic and senescent SMCs with aging/hypertension. We identified three sub-clusters of Spp1high synthetic SMCs, Spp1high matrix activated fibroblasts and Spp1high scar-associated macrophage involved in hypertensive aging, highlighting that Spp1, encoding protein osteopontin (OPN), could be a potential regulator participating in hypertensive aging. Spp1high scar-associated macrophage enriched for ROS metabolic process, supramolecular fiber organization and actin filament organization. Cell-cell communication analysis also revealed SPP1-Cd44 receptor pairing was markedly aggravated on hypertensive aging condition. Importantly, the concentration of OPN in human serum significantly potentiated in hypertension patient compared with normal group. Thus, we provide a comprehensive cell atlas to systematically resolve the cellular diversity and dynamic cellular communication changes of the vessel wall during hypertensive aging, highlight the mechanisms of vascular vasodilation through cGMP-PKG signaling pathway and identified a protein marker osteopontin as a potential regulator of vascular remodeling during hypertensive aging. Overall design: This entry contains 10x Single-cell RNA-seq data of FACS sorted nucleated living cells from aorta, femoral and mesentery artery of Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) aging 16-72 weeks.