Multiomics Investigation of the Hypertensive Human Heart

Biobanked, postmortem human heart tissue presents a unique opportunity to understand the pathogenesis of human cardiovascular disease risk factors through detailed multiomic analyses. We hypothesize that hypertension affects the cardiac transcriptome and cellular subtypes in a site-specific manner. We performed bulk and single-nucleus RNA-seq (snRNA-seq) on spatially distinct ventricular and atrial samples of postmortem hearts from donors with hypertension (n=3) and normotensive referents (n=2), using our rigorous cardiac dissection and preservation protocol. We identified both chamber- and cell-type specific transcriptomic profiles, including altered NAD+/NADH homeostasis and dysregulated metabolic gene expression. We identified a unique proliferative endothelial subtype in cardiac samples from donors with hypertension. Atrial contractile vascular smooth muscle cells were depleted in tissue from donors with hypertension compared to tissue from normotensive referents. Future studies are needed to understand the contributions of reductive stress and related signaling, and the contributions of unique endothelial and vascular smooth muscle cell states in hypertensive heart disease. Overall design: Cross-sectional study design consisting of atrial and ventricular cardiac samples collected postmortem from donors with (n = 3) and without (n = 2) systemic hypertension