Abstract 007: Hypertension-induced Neurovascular Dysfunction At Single-cell Resolution

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2022-09, Vol.79 (Suppl_1)
• Main Authors: Schaeffer, Samantha M, Santisteban, Monica M, Faraco, Giuseppe, Garcia-bonilla, Lidia, Anrather, Josef, Iadecola, Costantino
• Format: Article
• Language: English
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/hyp.79.suppl_1.007

Abstract only Hypertension (HTN) disrupts vital neurovascular control mechanisms, thereby increasing the brain’s susceptibility to vascular insufficiency, white matter lesions, and cognitive impairment. Yet, the distinct vascular, neuronal, and glial cell types targeted by HTN, as well as the ensuing cellular network disruption driving the neurovascular and cognitive deficits remain undefined. Here we sought to uncover transcriptomic changes in neurons and vascular cells using unbiased, single-cell RNA sequencing on the neocortex of 10-week old C57BL/6 male mice with angiotensin II (AngII) HTN. Vehicle or AngII (600ng/kg/min s.c.) were administered for 3 days, when blood-brain barrier (BBB) permeability start to increase, or 42 days, when neurovascular and cognitive dysfunction are fully developed (n=3/group). We analyzed 39,451 single-cell transcriptomes comprising 26 cell types. Surprisingly, 3 days of AngII induced significantly greater transcriptional changes in venular ECs compared to arteriolar ECs (EdgeR; pval< 0.05, logFC> 2), supporting the notion that venular ECs are uniquely sensitive to the early effects of HTN (Hypertension 76:795, 2020). Gene ontology analysis of differentially expressed genes prominently implicated altered venular immune signaling, BBB dysfunction, and, notably, a secretory phenotype characteristic of senescence (pval