Perivascular Fibroblast-Endothelium Interactions in Hypertension and Cerebral Ischemia

高血压和脑缺血中血管周围成纤维细胞-内皮细胞的相互作用

• 批准号: 10598600
• 负责人: Chia-Yi Kuan
• 金额: $ 20.19万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10598600
• 关键词: Acute; Affinity Chromatography; Age; Alzheimer' s Disease; Angiogenesis Inhibitors; Bioinformatics; Blood Vessels; Brain; Cell Communication; Cerebral Ischemia; Cerebral cortex; Cerebrum; Chronic; Cognition Disorders; Collagen; Common carotid artery; Contralateral; Data; Endothelial Cells; Endothelium; Extracellular Matrix; Fibroblasts; Gene Expression; Genes; Genomics; Goals; Hypertension; Impaired cognition; In Situ Hybridization; Inflammation; Inflammatory; Intervention; Ipsilateral; Ischemia; Matrix Metalloproteinases; Messenger RNA; Methods; Microvascular Dysfunction; Mus; Outcome; Oxidative Stress; Pathogenesis; Pathologic; Peptide Hydrolases; Process; Renin; Resistance; Ribosomes; Side; Smooth Muscle Myocytes; Stimulus; Testing; Time; Transcript; Transgenic Organisms; Translating; Vascular Cognitive Impairment; Vascular Endothelial Cell; Vascular Endothelium; Wild Type Mouse; angiogenesis; arteriole; artery occlusion; blood-brain barrier permeabilization; cell type; cerebrovascular; cognitive function; cytokine; density; differential expression; endothelial dysfunction; immunoregulation; insight; mouse model; new therapeutic target; novel; public health relevance; response; single-cell RNA sequencing; transcriptome; transcriptome sequencing; vascular injury

PROJECT SUMMARY (Description) Perivascular fibroblasts (PVFs) and vascular endothelium are important responders to hypertension and cerebral ischemia. Long-term aberrant interactions of PVFs and endothelium may also promote vascular cognitive disorders (VCD), but the mechanisms remain poorly understood. This project will use PVF-specific single-cell RNA-Seq and vascular endothelium-specific or TRAP-Seq to test the impacts of hypertension and cerebral ischemia on gene expression. Outcomes of this project may suggest novel therapeutic targets. Aim 1 will test the transcriptome changes of endothelial cells in a mouse model of chronic hypertension (ReninTg) with and without partial cerebral ischemia. Aim 2 will use bitransgenic ReninTg and Pdgfra-H2BGFP mice, with and without partial cerebral ischemia, to isolate PVFs for single-cell RNA-Seq comparison. In summary, this project will use open-ended genomic methods to correlate, for the first time, the transcriptome adaptations by PVFs and vascular endothelium to hypertension and combined hypertension/ischemia.

项目概述（描述）