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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...
February 27, 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...
February 3, 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...
April 15, 2016: 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...
February 23, 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
Jennifer K Trittmann, Julie M Gastier-Foster, Erik J Zmuda, Jessica Frick, Lynette K Rogers, Veronica J Vieland, Louis G Chicoine, Leif D Nelin
AIM: Pulmonary hypertension (PH) develops in 25-40% of bronchopulmonary dysplasia (BPD) patients, substantially increasing mortality. We have previously found that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) production, is elevated in patients with BPD-associated PH. ADMA is metabolised by N(ᴳ) ,N(ᴳ) -dimethylarginine dimethylaminohydrolase (DDAH). Presently, we test the hypothesis that there are single nucleotide polymorphisms (SNPs) in DDAH1 and/or DDAH2 associated with the development of PH in BPD patients...
April 2016: Acta Paediatrica
Lili Zhao, Yongmin Mao, Ying Zhang, Ying Shi, Yanqiu Song
OBJECTIVE: To investigate the therapeutic effect of Ad-hVEGF165 on the endothelial cells dysfunction induced by homocysteine (Hcy) and related molecular mechanisms. METHODS: Human umbilical vein endothelial cells CRL-1730 were treated with Hcy at different concentrations (0, 0.05, 1.00 mmol/L) for 24 h. The same concentration of Hcy, Ad-Track and Ad-hVEGF165 were added to the cells in the following groups: blank group, Hcy0.05 group, Hcy1.00 group, Ad-Track group, Hcy0...
May 2015: Zhonghua Xin Xue Guan Bing za Zhi
B A Lumicisi, J E Cartwright, K Leslie, A E Wallace, G S Whitley
STUDY QUESTION: Does inhibition of dimethylarginine dimethylaminohydrolase (DDAH) increase the sensitivity of trophoblasts to TRAIL-induced apoptosis? SUMMARY ANSWER: Inhibition of DDAH1, but not DDAH2, increases the sensitivity of trophoblasts to TRAIL-induced apoptosis. WHAT IS KNOWN ALREADY: Successful human pregnancy is dependent on adequate trophoblast invasion and remodelling of the maternal spiral arteries. Increased trophoblast apoptosis is seen in pregnancies complicated by pre-eclampsia...
August 2015: Human Reproduction
Yuan Li, Yan Ke, Jia-ye Jiang, Xiao-jun Li, Yong-bo Jiang
OJECTIVE: To observe the effect of tianma gouteng decoction (TGD) on the endothelial function and the renal protein expression of spontaneously hypertensive rats, and to analyze its possible mechanism. METHODS: Totally 18 6-week-old SHR were randomly divided into 3 groups according to randomized block design, the SHR control group, the TGD group, and the captopril group, 6 in each group. Meanwhile, Wistar Kyoto (WKY) rats of the same age were recruited as a WKY control group...
April 2015: Chinese Journal of Integrated Traditional and Western Medicine
J-H Wang, D Chen, K-Q Zhang, H Zhang, Q Fu
The effect of DDAH/ADMA/NOS pathway in penile tissue of rats of different age was investigated to better understand the mechanism of age-related erectile dysfunction (ED). The Sprague Dawley male rats were assigned as the young group (3 month old, n = 10) and the old group (18 month old, n = 10) respectively. Intracavernous pressure (ICP) was measured before and after papaverine intracavernous injection. Pathology structure of penile tissue was evaluated under transmission electron microscope. The expression amounts of asymmetric dimethylarginine (ADMA) and cyclic guanosine monophosphate (cGMP) in penile tissue were detected by ELISA; the expression levels of isoform-specific DDAH and NOS were assessed via Western blot...
April 2016: Andrologia
Simon Lambden, Peter Kelly, Blerina Ahmetaj-Shala, Zhen Wang, Benjamin Lee, Manasi Nandi, Belen Torondel, Matthew Delahaye, Laura Dowsett, Sophie Piper, James Tomlinson, Ben Caplin, Lucy Colman, Olga Boruc, Anna Slaviero, Lan Zhao, Eduardo Oliver, Sanjay Khadayate, Mervyn Singer, Francesca Arrigoni, James Leiper
OBJECTIVE: Nitric oxide is a key to numerous physiological and pathophysiological processes. Nitric oxide production is regulated endogenously by 2 methylarginines, asymmetric dimethylarginine (ADMA) and monomethyl-L-arginine. The enzyme that specifically metabolizes asymmetric dimethylarginine and monomethyl-L-arginine is dimethylarginine dimethylaminohydrolase (DDAH). The first isoform dimethylarginine dimethylaminohydrolase 1 has previously been shown to be an important regulator of methylarginines in both health and disease...
June 2015: Arteriosclerosis, Thrombosis, and Vascular Biology
Bethany K Redel, Kimberly J Tessanne, Lee D Spate, Clifton N Murphy, Randall S Prather
Culture systems promote development at rates lower than the in vivo environment. Here, we evaluated the embryo's transcriptome to determine what the embryo needs during development. A previous mRNA sequencing endeavour found upregulation of solute carrier family 7 (cationic amino acid transporter, y+ system), member 1 (SLC7A1), an arginine transporter, in in vitro- compared with in vivo-cultured embryos. In the present study, we added different concentrations of arginine to our culture medium to meet the needs of the porcine embryo...
May 2015: Reproduction, Fertility, and Development
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