Ceruloplasmin Mediated Penile Endothelial Dysfunction in Type 1 Diabetes

铜蓝蛋白介导的 1 型糖尿病阴茎内皮功能障碍

• 批准号: 7315369
• 负责人: Kanchan Chitaley Schindlauer
• 金额: $ 23.4万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-13 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7315369
• 关键词: Acute; Age; American; Aorta; Binding; Biochemical; Biological Availability; Blood Vessels; Cardiovascular system; Cell membrane; Ceruloplasmin; Condition; Copper; Diabetes Mellitus; Diabetic Angiopathies; Diabetic mouse; Endothelium; Erectile dysfunction; Functional disorder; Gel; Gene Expression; Generations; Healthcare; Hyperglycemia; In Vitro; Incidence; Injection of therapeutic agent; Insulin-Dependent Diabetes Mellitus; Intervention; Lead; Life; Measurement; Mediating; Medical; Microarray Analysis; Modeling; Mus; Oryctolagus cuniculus; Oxidative Stress; Patients; Penile Erection; Physiological; Physiology; Population; Prevalence; Prevention; Production; Proteins; Public Health; Reactive Oxygen Species; Relaxation; Reporting; Resources; Risk; Role; Smooth Muscle; Streptozocin; Superoxides; Testing; Therapeutic; Time; Tissues; United States; Vasodilation; Vasodilation disorder; aged; base; care seeking; cohort; diabetic; diabetic rat; early onset; gain of function; health care service utilization; improved; in vivo; in vivo Model; insight; loss of function; men; mouse model; non-diabetic; pressure; prevent; response; satisfaction; success

DESCRIPTION (provided by applicant): Diabetes uniquely impacts all components of the erectile response, and all co-morbid medical conditions, imparts the greatest risk of ED. In that population based analysis of OS men aged 20 and up, 49% of all men with diabetes reported ED. Furthermore, men with diabetes utilize more health care resources for ED treatment than men without diabetes, and the incidence of diabetes if increasing. In addition to the increased prevalence of ED in the diabetic population, the onset of ED in this cohort is up to 10-15 years earlier than in the g~neral population. This is particularly relevant because younger men are more likely to seek care and utilize health care resources for the treatment of ED. Thus, interventions to improve or prevent ED in men with diabetes will become increasingly important. To test our general hypothesis that increased tissue specific penile expression of ceruloplasmin in diabetes results in impaired cavernosal vasodilation and penile endothelial dysfunction, we will complete the following specific aims: (1) determine if ceruloplasmin inhibits NO bioavailability through the inhibition of eNOS activity, 2) determine the role of ceruloplasmin on penile vascular endothelial function in vivo, 3) investigate whether ceruloplasmin causes impaired penile erection in a mouse model of type 1 diabetes. Relevance to Public Health: Treatment or prevention of ED in men with diabetes is necessary to improve life satisfaction and reduce the utilization of health care resources in this rapidly growing portion of the American population. Relevance to Public Health: Treatment or prevention of ED in men with diabetes is necessary to improve life satisfaction and reduce the utilization of health care resources in this rapidly growing portion of the American population.

描述(由申请人提供)：糖尿病对勃起反应的所有组成部分都有独特的影响，所有并存的医疗条件都会带来勃起功能障碍的最大风险。在对20岁及以上的OS男性进行的基于人群的分析中，49%的糖尿病男性报告了ED。此外，患有糖尿病的男性在ED治疗上使用的卫生保健资源比没有糖尿病的男性更多，糖尿病的发病率也在增加。除了糖尿病人群中ED的患病率增加外，这一队列中的ED的发病时间比普通人群早10-15年。这一点特别重要，因为年轻男性更有可能寻求护理并利用卫生保健资源治疗ED。因此，改善或预防糖尿病男性勃起功能障碍的干预措施将变得越来越重要。为了验证我们的一般假设，即糖尿病患者阴茎组织特异性铜蓝蛋白表达增加会导致海绵体血管扩张受损和阴茎内皮功能障碍，我们将完成下列特定目标：(1)确定铜蓝蛋白是否通过抑制eNOS活性而抑制NO的生物利用度；2)确定铜蓝蛋白在体内对阴茎血管内皮功能的作用；3)研究铜蓝蛋白是否能导致1型糖尿病小鼠勃起功能受损。与公共卫生的相关性：在快速增长的美国人口中，治疗或预防男性糖尿病患者的ED对于提高生活满意度和减少卫生保健资源的使用是必要的。与公共卫生的相关性：在快速增长的美国人口中，治疗或预防男性糖尿病患者的ED对于提高生活满意度和减少卫生保健资源的使用是必要的。