Glomerular COX-2 in Hypertensive Renal Disease

高血压肾病中的肾小球 COX-2

• 批准号: 7285217
• 负责人: EDGAR A JAIMES
• 金额: $ 14.36万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-20 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7285217
• 关键词: Ablation; Angiotensin II; Cell Proliferation; Chronic Kidney Failure; Clinical; Congestive Heart Failure; Coronary Arteriosclerosis; Dahl Hypertensive Rats; Data; Deposition; Development; Diabetes Mellitus; End stage renal failure; Enzymes; Etiology; Extracellular Matrix; Generations; Goals; Growth; Growth Factor; Health; Heart Diseases; Hypertension; Hypertrophy; Immunohistochemistry; In Vitro; Incidence; Inflammatory; Injury; Kidney; Kidney Diseases; Knowledge; Lead; Mediating; Mediator of activation protein; Microcirculation; Modeling; Morbidity - disease rate; Organ; Outcome; Pathogenesis; Peripheral Vascular Diseases; Personal Satisfaction; Play; Prevalence; Production; Prostaglandins; Public Health; Rate; Rattus; Reactive Oxygen Species; Renin-Angiotensin System; Research; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Role; Series; Signal Transduction; Sodium Chloride; Stimulus; Stroke; Transforming Growth Factor beta; United States; Up-Regulation; Vasoconstrictor Agents; Western Blotting; base; cost; cyclooxygenase 2; cytokine; hemodynamics; hypertension treatment; in vivo; mesangial cell; mortality; novel strategies; prevent; progesterone 11-hemisuccinate-(2-iodohistamine); research study; response; salt sensitive; urinary tract obstruction

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) is a major health problem associated with a high morbidity and mortality. Hypertension is a major risk factor for the development of CKD. Maladpative activation of the renin angiotensin system (RAS) has been shown to play a critical role in the pathogenesis of CKD of different etiologies including hypertension. Our long term objective is to such as TGF-B. We also hypothesize that COX-2 derived PCs play a major role in the pathogenesis of end-organ injury in hypertension, specifically renal injury. We will pursue the following specific aims: Aim 1: To identify the mechanisms by which Angiotensin II (Ang II) induces COX-2 expression and activity in the glomerulus. To take this aim to completion we will use a series of in vitro and in vivo experiments aimed at determining the role of reactive oxygen species (ROS) and TGF-beta as mediators of the glomerular COX-2 expression in response to Ang II. Aim 2: To identify the role of COX-2 derived PCs in the pathogenesis of glomerular injury associated with activation of the renin angiotensin system. We will determine the effects of COX-2 blockade on the growth promoting effects of Ang II in cultured mesangial cells including extracellular matrix (ECM) deposition and mesangial cell proliferation. In addition, we will identify the role of COX-2 in the hypertensive Dahl salt sensituive rat rat, a model of functional upregulation of Ang II, increased ROS generation and severe end-organ injury. We will determine the glomerular expression of COX-2 in hypertensive Dahl salt sensitive rats (RT-PCR, western blot and immunohistochemistry) as well as the effects of COX-2 blockade on glomerular injury in this model of salt sensitive hypertension. Results from these studies will enhance our understanding of the role of RAS activation and COX-2 in the pathogenesis of CKD.

描述（由申请人提供）：慢性肾脏疾病（CKD）是一种与高发病率和死亡率相关的主要健康问题。高血压是CKD发展的主要危险因素。肾素血管紧张素系统（RAS）的异常激活已被证明在包括高血压在内的不同病因的CKD的发病机制中起关键作用。我们的长期目标是如TGF-B。我们还推测考克斯-2衍生的PC在高血压终末器官损伤，特别是肾损伤的发病机制中起主要作用。我们将追求以下具体目标：目的1：确定血管紧张素II（Ang II）诱导肾小球考克斯-2表达和活性的机制。为了完成这一目标，我们将使用一系列体外和体内实验，旨在确定活性氧（ROS）和TGF-β作为肾小球考克斯-2表达的介导剂对Ang II的反应。目的2：研究考克斯-2衍生的前体细胞在肾小球损伤中的作用。我们将确定考克斯-2阻断对血管紧张素II在培养的系膜细胞中的生长促进作用的影响，包括细胞外基质（ECM）沉积和系膜细胞增殖。此外，我们将确定考克斯-2在高血压Dahl盐敏感大鼠中的作用，这是一种Ang II功能上调、ROS产生增加和严重终末器官损伤的模型。我们将通过RT-PCR、免疫印迹和免疫组化等方法检测考克斯-2在高血压盐敏感大鼠肾小球中的表达，并观察考克斯-2阻断剂对盐敏感性高血压大鼠肾小球损伤的影响。这些研究的结果将加深我们对RAS激活和考克斯-2在CKD发病机制中的作用的理解。

项目成果

Dissociation between metabolic and vascular insulin resistance in aging.

• DOI: 10.1152/ajpheart.00138.2007
• 发表时间: 2007-07
• 期刊: American journal of physiology. Heart and circulatory physiology
• 作者: I. Schulman;Ming-Sheng Zhou;E. Jaimes;L. Raij

Nicotine: the link between cigarette smoking and the progression of renal injury?

• DOI: 10.1152/ajpheart.00693.2006
• 发表时间: 2007-01-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
• 影响因子: 4.8
• 作者: Jaimes, Edgar A.;Tian, Run-Xia;Raij, Leopoldo
• 通讯作者: Raij, Leopoldo

Benazepril combined with either amlodipine or hydrochlorothiazide is more effective than monotherapy for blood pressure control and prevention of end-organ injury in hypertensive Dahl rats.

贝那普利与氨氯地平或氢氯噻嗪联合使用比单一疗法更有效地控制高血压 Dahl 大鼠的血压和预防终末器官损伤。

• DOI: 10.1097/01.fjc.0000238598.09152.30
• 发表时间: 2006
• 期刊: Journal of cardiovascular pharmacology.
• 作者: Zhou,Ming-Sheng;Jaimes,EdgarA;Raij,Leopoldo
• 通讯作者: Raij,Leopoldo

A case of Weber-Christian disease with collapsing glomerulopathy.

韦伯-克里斯蒂安病伴塌陷性肾小球病一例。

• DOI: 10.1053/j.ajkd.2006.05.025
• 发表时间: 2006
• 期刊: American journal of kidney diseases : the official journal of the National Kidney Foundation.
• 作者: Nahar,Nilay;Pardo,Victoriano;Sadhu,Sanghamitra;Young,Larry;Gonzalez,Nora;Jaimes,EdgarA
• 通讯作者: Jaimes,EdgarA

Thiazide diuretics, endothelial function, and vascular oxidative stress.

噻嗪类利尿剂、内皮功能和血管氧化应激。

• DOI: 10.1097/hjh.0b013e3282f3e39d
• 发表时间: 2008
• 期刊: Journal of hypertension
• 影响因子: 4.9
• 作者: Zhou,Ming-Sheng;Schulman,IvonneHernandez;Jaimes,EdgarA;Raij,Leopoldo
• 通讯作者: Raij,Leopoldo