Retinal vasculature in hypertension

高血压患者的视网膜血管

基本信息

批准号：
10367158
负责人：
NORMAN R HARRIS
金额：
$ 36.5万
依托单位：
LOUISIANA STATE UNIV HSC SHREVEPORT
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：
2022-09-30 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10367158
关键词：
Address Adhesions Adult Angiotensin II Antihypertensive Agents Area Basement membrane Blood Platelets Blood Pressure Blood Vessels Blood capillaries Blood flow Blood-Retinal Barrier CD31 Antigens Chronic Collagen Connexin 43 Data Dependence Desmin Development Disease E-Selectin Endothelial Cells Endothelin-1 Endothelium Event Extracellular Matrix Eye Female Fibronectins Functional disorder Future Glycocalyx Glycoproteins Glypican Gonadal Steroid Hormones Health Hemorrhage Hypertension Hypertensive Retinopathy Hypoxia Inbred SHR Rats Inbred WKY Rats KDR gene Knowledge Lead Leukocytes Mediator of activation protein Mesenchymal Microcirculation Modeling Molecular N-Cadherin Names Optic Disk Oxygen Pathologic Pathway interactions Perfusion Pharmaceutical Preparations Pharmacology Phenotype Platelet Glycoproteins Population Predisposition Prevalence Proteoglycan Recovery Retina Retinal Artery Occlusion Retinal Diseases Risk Factors S100A4 gene Smooth Muscle Smooth Muscle Myocytes Surface Swelling Testing Thinness Thrombus United States Vasodilation Vimentin Vision Work arteriole blood pressure reduction cadherin 5 collagenase cotton wool spots driving force endothelial dysfunction experimental study hypertensive male moesin muscle degeneration negative affect normotensive novel pressure prevent response retina blood vessel structure retina circulation retinal neuron sex syndecan therapeutically effective vein occlusion von Willebrand factor receptor

项目摘要

Approximately 32-44% of the adult US population has hypertension, with one of the many complications being hypertensive retinopathy. In one study, the prevalence of retinopathy was found to be 85% amongst those with severe hypertension, and 25% for those with mild hypertension. Retinal consequences of hypertension include arteriolar narrowing, hemorrhages, cotton wool spots (localized hypoxia), and optic disk swelling. Other retinal changes include hyalinization of arteriolar walls, thickening of the vascular basement membrane, closure of capillaries, smooth muscle degeneration, and blood-retinal barrier dysfunction. Additionally, hypertension is a major risk factor for the highly threatening events of retinal artery or vein occlusion. The primary treatment for hypertensive retinopathy is to reduce blood pressure; however, consequences of the disease including narrowing of arterioles persist even following anti-hypertension medication. Therefore, a better knowledge of the mechanisms of the disease could lead to the development of additional and more effective therapeutic options. Our overall hypothesis is that the vascular complications of hypertensive retinopathy are due phenotypic changes in endothelial and smooth muscle cells, with vessel wall remodeling limiting recovery even with anti-hypertensive medication. The specific aims are to: (1) determine the sex-dependent expression of the glycocalyx in the retina, and determine the consequences of hypertension on this expression, (2) examine the sex-dependent expression of platelet endothelial adhesion molecule-1 and vascular endothelial cadherin in the retina, and test the hypothesis that changes in these junctional molecules in the hypertensive retina are due to endothelial-to- mesenchymal transition, and (3) test the hypothesis that remodeling of blood vessel walls in the SHR retina induces susceptibility to poor retinal perfusion when high blood pressure is reduced to normal.

大约 32-44% 的美国成年人患有高血压，这是众多并发症之一是高血压性视网膜病变。一项研究发现，视网膜病变的患病率为 85% 重度高血压患者占25%，轻度高血压患者占25%。视网膜后果高血压包括小动脉狭窄、出血、棉絮斑（局部缺氧）和视神经椎间盘肿胀。其他视网膜变化包括小动脉壁玻璃样变、血管增厚基底膜、毛细血管闭合、平滑肌变性和血视网膜屏障功能障碍。此外，高血压是视网膜动脉高度威胁事件的主要危险因素或静脉阻塞。高血压性视网膜病变的主要治疗方法是降低血压；然而，即使在抗高血压治疗后，疾病的后果（包括小动脉狭窄）仍然存在药物。因此，更好地了解该疾病的机制可能会导致疾病的发展额外和更有效的治疗选择。我们的总体假设是，血管高血压视网膜病变的并发症是由于内皮细胞和平滑肌的表型变化所致细胞，即使使用抗高血压药物，血管壁重塑也会限制恢复。具体的目的是：（1）确定视网膜中糖萼的性别依赖性表达，并确定高血压对此表达的影响，（2）检查血小板的性别依赖性表达视网膜中的内皮粘附分子-1和血管内皮钙粘蛋白，并检验假设高血压视网膜中这些连接分子的变化是由于内皮细胞与间充质转化，以及（3）检验 SHR 视网膜中血管壁重塑的假设当高血压降至正常时，会导致视网膜灌注不良。