Retinal vasculature in hypertension

高血压患者的视网膜血管

• 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
• 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

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，并伴有多种并发症之一 高血压性视网膜病变在一项研究中，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%。视网膜的后果 高血压包括小动脉狭窄、血管扩张、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，血管壁增厚， 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，高血压是高度威胁性视网膜动脉事件的主要危险因素 或静脉闭塞。高血压视网膜病变的主要治疗方法是降低血压;然而， 即使在抗高血压药物治疗后， 药因此，更好地了解疾病的机制可能会导致发展 更多更有效的治疗选择我们的总体假设是 高血压视网膜病变的并发症是由于内皮和平滑肌的表型变化 细胞，血管壁重塑限制恢复，即使使用抗高血压药物。具体 目的是：（1）确定视网膜中糖萼的性别依赖性表达，并确定 高血压对血小板表达的影响;（2）检测血小板表达的性别依赖性 内皮细胞粘附分子-1和血管内皮细胞钙粘蛋白在视网膜中的表达，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对 间充质转化，和（3）测试的假设，血管壁重塑在SHR视网膜 当高血压降低到正常时，诱导对不良视网膜灌注的易感性。