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Mei-Rong Du, Li Yan, Nian-Sheng Li, Yu-Jie Wang, Ting Zhou, Jun-Lin Jiang
Diabetic retinopathy (DR) is a leading cause of vision loss with retinal neovascularization. This study aims to investigate whether Asymmetric dimethylarginine (ADMA) impacts the pathogenesis of DR via focusing on promoting retinal neovascularization and its underlying molecular mechanisms. Diabetic rats were induced by a single intraperitoneal injection of streptozotocin (STZ) for 20 weeks. ADMA levels in aqueous and the influence of hypoxia on ADMA and angiogenesis in RF/6A cells were examined. The effects and underlying molecular mechanisms of ADMA on neovascularization of RF/6A cells were further evaluated by administration of ADMA, DDAH siRNA or ephrinB2 siRNA...
May 16, 2018: Vascular Pharmacology
Hong-Bo Xiao, Guo-Guang Sui, Xiang-Yang Lu, Zhi-Liang Sun
Chronic endometritis is a continuous inflammation of uterine endometrium. Recent research has shown that higher asymmetric dimethylarginine (ADMA) levels contribute to endothelial dysfunction. In the present study, we tested whether there is a correlation between endometritis and ADMA in LPS-induced endometritis rat and the mechanisms involved. Thirty-six rats were divided into two groups: blank control group and rat model of endometritis group. The entire infused uterus were removed to observe the changes of histopathology, production of myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, 8-isoprostane, and reactive oxygen species (ROS), and gene expression of dimethylarginine dimethylaminohydrolase 2 (DDAH2), protein-methyl transferase 1 (PRMT1), TNF-α, and IL-6...
February 2018: Inflammation
Ana Maria Milanez Azevedo, Guilhermo Brites-Anselmi, Lucas Cezar Pinheiro, Vanessa de Almeida Belo, Fernanda Borchers Coeli-Lacchini, Carlos Augusto Fernandes Molina, Murilo Ferreira de Andrade, Silvio Tucci, Emilio Hirsch, Jose Eduardo Tanus-Santos, Riccardo Lacchini
Sildenafil is the most used treatment of erectile dysfunction, however a large part of patients do not respond to therapy. This drug enhances nitric oxide (NO) signaling, and therefore factors that alter NO production may impact this drug responsiveness. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of all NO synthases, and is metabolized by Dimethylarginine Dimethilaminohydrolase (DDAH) 1 and 2. Here we aimed to assess the relationship between plasma levels of ADMA and nitrite (marker of nitric oxide production) with Sildenafil responsiveness...
December 1, 2017: Nitric Oxide: Biology and Chemistry
Meera B Krishna, Annu Joseph, Philip Litto Thomas, Belinda Dsilva, Sathy M Pillai, Malini Laloraya
BACKGROUND: Though oxidative stress is associated with Polycystic Ovary Syndrome (PCOS), the status of nitric oxide is still unclear. Nitric Oxide (NO) plays pivotal roles in many physiological functions which are compromised in PCOS. Our recent study reveals lowered T-regulatory cells (Tregs) in PCOS, and Treg generation is known to be regulated by NO levels. However concrete evidences are lacking on mechanisms modulating NO levels under PCOS. METHODS: This is a retrospective case-control cohort study, comprised of PCOS women (N=29) and normal menstruating women as controls (N=20)...
2017: Cellular Physiology and Biochemistry
Chang-Wu Lu, Yuan Lin, Yan-Ping Lei, Lan Wang, Zhi-Min He, Yan Xiong
OBJECTIVE: Endothelial dysfunction plays a pivotal role in the development of diabetic cardiovascular complications. Accumulation of endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) and inhibition of dimethylarginine dimethylaminohydrolase (DDAH) activity have been involved in diabetic endothelial dysfunction. This study was to investigate the effect of pyrrolidine dithiocarbamate (PDTC) on impairment of endothelium-dependent vasodilatation in diabetic rats and its potential mechanism...
2017: PloS One
Martin Sebastian Winkler, Stefan Kluge, Maximilian Holzmann, Eileen Moritz, Linda Robbe, Antonia Bauer, Corinne Zahrte, Marion Priefler, Edzard Schwedhelm, Rainer H Böger, Alwin E Goetz, Axel Nierhaus, Christian Zoellner
BACKGROUND: Nitric oxide (NO) regulates processes involved in sepsis progression, including vascular function and pathogen defense. Direct NO measurement in patients is unfeasible because of its short half-life. Surrogate markers for NO bioavailability are substrates of NO generating synthase (NOS): L-arginine (lArg) and homoarginine (hArg) together with the inhibitory competitive substrate asymmetric dimethylarginine (ADMA). In immune cells ADMA is cleaved by dimethylarginine-dimethylaminohydrolase-2 (DDAH2)...
July 15, 2017: Critical Care: the Official Journal of the Critical Care Forum
Tao Wang, Yan Zhang, Kai Niu, Lijun Wang, Yanan Shi, Bing Liu
We investigated the association of the -449G/C and -1151A/C polymorphisms in the DDAH2 gene with plasma asymmetric dimethylarginine (ADMA) concentration and erythropoietin resistance in 131 Chinese patients on maintenance hemodialysis (MHD). The -449G allele was in complete linkage disequilibrium with the -1151A allele and so were their corresponding C alleles. The -449GG/-1151AA genotype had the highest plasma ADMA concentration, erythropoietin resistance index (EPI) and serum malondialdehyde level, compared to either the -449GC/-1151AC or -449CC/-1151CC variation...
September 2017: Clinical and Experimental Pharmacology & Physiology
Zhaoya Liu, Yanbo Liu, Qian Xu, Haiyang Peng, Yixin Tang, Tianlun Yang, Zaixin Yu, Guangjie Cheng, Guogang Zhang, Ruizheng Shi
Vascular peroxidase 1 (VPO1) is a member of the peroxidase family which aggravates oxidative stress by producing hypochlorous acid (HOCl). Our previous study demonstrated that VPO1 plays a critical role in endothelial dysfunction through dimethylarginine dimethylaminohydrolase2 (DDAH2)/asymmetric Dimethylarginine (ADMA) pathway. Hereby we describe the regulatory role of VPO1 on endothelial nitric oxide synthase (eNOS) expression and activity in human umbilical vein endothelial cells (HUVECs). In HUVECs AngiotensinII (100nM) treatment reduced Nitric Oxide (NO) production, decreased eNOS expression and activity, which were reversed by VPO1 siRNA...
August 2017: Redox Biology
Yuan Lin, Mei Feng, Chang-Wu Lu, Yan-Ping Lei, Zhi-Min He, Yan Xiong
Endothelial dysfunction plays a pivotal role in the pathogenesis of atherosclerosis. Endogenous inhibitor of nitric oxide synthase (NOS) asymmetric dimethylarginine (ADMA) has been recognized as an independent risk factor of endothelial dysfunction and the biomarker of atherosclerosis. This study was to investigate whether endogenous ADMA and its metabolic enzyme dimethylarginine dimethylaminohydrolase (DDAH) were involved in mechanisms of captopril protection against endothelial dysfunction in high fat diet feeding rabbits...
March 5, 2017: European Journal of Pharmacology
Sara Shoeibi, Shabnam Mohammadi, Hamid Reza Sadeghnia, Elahe Mahdipour, Majid Ghayour-Mobarhan
The in vitro amplification of endothelial progenitor cells (EPCs) is an important method because of its role in gene transferring and regenerative medicine. In this study, we isolated rabbit bone marrow-derived EPCs to further manipulation and overexpression of dimethylarginine dimethylaminohydrolase (DDAH) in EPCs. Isolated EPCs were cultured, expanded in endothelial basal medium. Morphology of EPCs and expression levels of surface markers detected using immunocytochemistry staining and through the use of flow cytometery...
March 2017: Cell Biochemistry and Function
Ru Zhou, Ping Ma, Aiqin Xiong, Yehua Xu, Yang Wang, Qingbin Xu
AIMS: Cardiovascular disease is the leading cause of death with high morbidity and mortality, and chronic heart failure is the terminal phase of it. This study aimed to investigate the protective effects of the low-dose rosuvastatin on isoproterenol-induced chronic heart failure and to explore the possible related mechanisms. METHODS: Male Sprague Dawley rats were given isoproterenol 5 mg/kg once a day for 7 days to establish heart failure model by subcutaneous injection...
April 2017: Cardiovascular Therapeutics
S L Gao, L Li, X J Zhai, R W Guo, S S Gao
OBJECTIVE: To investigate the effects and related mechanism of 5-aza-2'-deoxycytidine(Aza) on endothelial function in Hyperhomocysteinemia rats. METHODS: Adult male SD rats were divided into 3 groups (n=7 each): control group, hyperhomocysteinemia (HHcy) group and Aza group according to the random number table. Control group rats were fed with normal diet. HHcy group rats were fed with diet adding 3% L-methionine. Aza group rats were fed with diet adding 3% L-methionine and Aza (0...
August 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
S Lambden, D Martin, K Vanezis, B Lee, J Tomlinson, S Piper, O Boruc, M Mythen, J Leiper
BACKGROUND: Tissue hypoxia is a cardinal feature of inflammatory diseases and modulates monocyte function. Nitric oxide is a crucial component of the immune cell response. This study explored the metabolism of the endogenous inhibitor of nitric oxide production asymmetric dimethylarginine(ADMA) by monocyte dimethylarginine dimethylaminohydrolase 2(DDAH2), and the role of this pathway in the regulation of the cellular response and the local environment during hypoxia. METHODS: Peritoneal macrophages were isolated from a macrophage-specific DDAH2 knockout mouse that we developed and compared with appropriate controls...
August 31, 2016: Nitric Oxide: Biology and Chemistry
Clemens Lange, Freya Mowat, Haroon Sayed, Manjit Mehad, Lucie Duluc, Sophie Piper, Ulrich Luhmann, Manasi Nandi, Peter Kelly, Alexander Smith, Robin Ali, James Leiper, James Bainbridge
Ischemia-induced angiogenesis is critical for tissue repair, but aberrant neovascularization in the retina causes severe sight impairment. Nitric oxide (NO) has been implicated in neovascular eye disease because of its pro-angiogenic properties in the retina. Nitric oxide production is inhibited endogenously by asymmetric dimethylarginines (ADMA and L-NMMA) which are metabolized by dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2. The aim of this study was to determine the roles of DDAH1, DDAH2, ADMA and L-NMMA in retinal ischemia-induced angiogenesis...
June 2016: Experimental Eye Research
Dong Chen, Ke-Qin Zhang, Bo Li, Ding-Qi Sun, Hui Zhang, Qiang Fu
Aging-related ED is predominantly attributed to neurovascular dysfunction mediated by NO suppression and increased oxidative stress in penis. The alterations of protein arginine methyltransferases 1 (PRMT1)/dimethylarginine dimethylaminohydrolase (DDAH)/asymmetrical dimethylarginine (ADMA)/NO synthase (NOS) pathway regulate NO production in the vascular endothelium. Epigallocatechin-3-gallate (EGCG) is one of the most abundant and antioxidative ingredients isolated from green tea. In the present study, 40 Sprague-Dawley rats were randomly distributed into four groups: one young rat group and three aged rat groups treated with daily gavage feedings of EGCG at doses of 0, 10 mg kg-1 and 100 mg kg-1 for 12 weeks, respectively...
May 2017: Asian Journal of Andrology
Yonghong Tan, Qiong Wang, Baisong Zhao, Yingjun She, Xiaobao Bi
Lidocaine has been recognized to induce neurotoxicity. However, the molecular mechanism underlying this effect, especially the critical molecules in cells that mediated the lidocaine-induced apoptosis were unclear. In the present study, PC12 cells were administrated with lidocaine for 48h. Using MTT assay and flow cytometry, we found lidocaine significantly decreased the cell proliferation and S phases in PC12 cells with treatment concentrations, and significantly enhanced cell apoptosis with treatment concentrations...
May 2016: Neurotoxicology
Yan Wu, Jie-Jie Zhang, Ting-Bo Li, Wei-Qi Liu, Lian-Sheng Li, Xiu-Ju Luo, Jun-Lin Jiang, Qi-Lin Ma, Zhi-Chun Yang, Jun Peng
Suppression of dimethylarginine dimethylaminohydrolase (DDAH) activation is related to endothelial dysfunction in hyperlipidemia, and nonmuscle myosin regulatory light chain (nmMLC20 ) has been show to exert transcriptional function in regulation of gene expression. This study aims to explore whether the suppression of DDAH activation promotes endothelial injury under the condition of hyperlipidemia and whether nmMLC20 can regulate DDAH expression in a phosphorylation-dependent manner. The rats were fed with high-fat diet for 8 weeks to establish a hyperlipidemic model, which showed an increase in plasma lipids and endothelial injury, accompanied by an elevation in myosin light chain kinase (MLCK) activity, phosphorylated nmMLC20 (p-nmMLC20 ) level, and asymmetric dimethylarginine (ADMA) content as well as a reduction in DDAH2 expression, DDAH activity, and nitric oxide (NO) content...
November 2016: Journal of Cardiovascular Pharmacology and Therapeutics
Nan Jiang, Min Wang, Jiayi Song, Yan Liu, Hongen Chen, Di Mu, Min Xia
SCOPE: Epidemiological studies have demonstrated that N-methylnicotinamide (MNA) may exert antithrombotic and anti-inflammatory effects on the endothelium. However, the exact role of MNA in endothelial function remains uncertain. METHODS AND RESULTS: Apolipoprotein E-deficient (apoE(-/-) ) mice fed with a high-fat, high-cholesterol diet (HCD) and human umbilical vein endothelial cells (HUVECs) were used to explore the role of MNA in endothelial function and its underlying mechanism...
July 2016: Molecular Nutrition & Food Research
Zhong Wang, Shaoze Chen, Lina Zhang, Guilin Lu, Chengming Zhou, Dao Wen Wang, Li Wang, Bayinbate Badengmu, Zhihong Zhai, Lian Qin
CONTEXT AND OBJECTIVE: Dimethylarginine dimethylaminohydrolase enzymes (DDAH), which are encoded by the genes DDAH1 and DDAH2, play a fundamental role in maintaining endothelial function. We conducted a case-control study on a Chinese population that included three ethnic groups (Han, Kazakh and Uygur), to systemically investigate associations between variations in the genes DDAH1 and DDAH2 and hypertension. DESIGN AND SETTING: Experimental study at the Department of Internal Medicine and Genetic Diagnosis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology...
January 19, 2016: São Paulo Medical Journal, Revista Paulista de Medicina
X Xu, X-Y Yang, B-W He, W-J Yang, W-W Cheng
OBJECTIVES: To investigate the expression levels of neuropilin 1 (NRP1) and vascular endothelial growth factor (VEGF) in the placentas of women with pre-eclampsia (PE), determine whether homocysteine (Hcy) contributes to the development of PE in mice, and detect alterations in placental NRP1 and VEGF in Hcy-treated mice. STUDY DESIGN: Placental tissue samples were obtained from 16 patients with and without PE. Using reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis, the expression levels of NRP1 and VEGF in PE and control placental tissues were examined...
January 2016: European Journal of Obstetrics, Gynecology, and Reproductive Biology
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