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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

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

项目总结(说明) 血管周围成纤维细胞(PVF)和血管内皮细胞是高血压和高血压的重要反应者脑缺血。PVF和内皮的长期异常相互作用也可能促进血管认知障碍(VCD)，但其机制仍知之甚少。该项目将使用特定于PVF的单细胞RNA-Seq和血管内皮细胞特异性或TRAP-Seq来测试高血压和高血压的影响脑缺血对基因表达的影响。该项目的结果可能会提出新的治疗靶点。目的1检测慢性高血压小鼠模型血管内皮细胞转录组的变化 (ReninTg)伴和不伴部分脑缺血。 AIM 2将使用双基因ReninTg和PDGFRA-H2BGFP小鼠，在部分脑缺血和不部分脑缺血的情况下，分离PVF，用于单细胞RNA-Seq比对。总而言之，该项目将首次使用开放式基因组方法来关联转录组 PVF和血管内皮细胞对高血压及其合并高血压/缺血的适应性。