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PAD AND nitric oxide

Sebastian Steven, Andreas Daiber, Jörn F Dopheide, Thomas Münzel, Christine Espinola-Klein
Reactive oxygen and nitrogen species (ROS and RNS, e.g. H2O2, nitric oxide) confer redox regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. At higher concentrations, ROS and RNS lead to oxidative stress and oxidative damage of biomolecules (e.g. via formation of peroxynitrite, fenton chemistry). Peripheral artery disease (PAD) is characterized by severe ischemic conditions in the periphery leading to intermittent claudication and critical limb ischemia (end stage)...
August 2017: Redox Biology
Muzaffer Akkoca, Suzan Emel Usanmaz, Cuneyt Koksoy, Ugur Bengisun, Emine Demirel-Yilmaz
At present there is no widely accepted biomarker for monitoring of vascular functions. The purpose of this prospective study was to investigate the association of some blood biomarkers with vascular reactivity in patients with peripheral arterial diseases (PAD). A prospective evaluation was made of 3 groups comprising a control group of healthy individuals, and patients with PAD caused by either atherosclerosis or Buerger's disease. Microvascular perfusion was examined using laser Doppler imaging of cutaneous erythrocyte flux after iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP)...
2017: Clinical Hemorheology and Microcirculation
Michèle Brix, Eva-Elina Buschmann, Andreas Zietzer, Jonnel Anthony Jaurigue, Lulu Li, Constantin Jungk, Ivo Buschmann, Doreen Janke, Philipp Hillmeister
BACKGROUND: Individual shear rate therapy (ISRT) has been designed as a novel non-invasive treatment option for peripheral artery disease (PAD) patients and has been shown to improve endothelial function and walking distance. The aim of this study was to elucidate the impact of ISRT on the level of nitric oxide in patient blood plasma and the expression of related molecular markers in peripheral blood mononuclear cells (PBMCs). Molecular diagnostic tests were performed for two ISRT trials...
January 2017: VASA. Zeitschrift Für Gefässkrankheiten
Victor Costa Castro-Alves, Daniel Gomes, Nelson Menolli, Maurício Luís Sforça, João Roberto Oliveira do Nascimento
Polysaccharides from a number of mushroom species are recognized as functional food ingredients with potential health benefits, including immunomodulatory effects. In this study, polysaccharides extracted from the basidiome with cold water (BaCW), hot water (BaHW), and hot alkali (BaHA) solution, and exo- (MyEX) and endopolysaccharides (MyEN) from the submerged culture of Pleurotus albidus, a promising species for farming and biomass production, were analyzed for their chemical composition and structure and immunomodulatory effects on macrophages...
February 2017: International Journal of Biological Macromolecules
Oliver A Stone, James G Carter, P Charles Lin, Ewa Paleolog, Maria J C Machado, David O Bates
KEY POINTS: Combining nitric oxide (NO)-mediated increased blood flow with angiopoietin-1-Tie2 receptor signalling induces arteriolargenesis - the formation of arterioles from capillaries - in a model of physiological angiogenesis. This NO-Tie-mediated arteriolargenesis requires endogenous vascular endothelial growth factor (VEGF) signalling. Inhibition of VEGF signalling increases pericyte coverage in microvessels. Together these findings indicate that generation of functional neovasculature requires close titration of NO-Tie2 signalling and localized VEGF induction, suggesting that the use of exogenous VEGF expression as a therapeutic for neovascularization may not be successful...
March 1, 2017: Journal of Physiology
J He, Y Jiang, P G Alexander, V Ulici, Y Zhu, S Wu, R S Tuan
OBJECTIVES: The infrapatellar fat pad (IPFP), which is located underneath the patella, close to cartilage surfaces, functions in distributing mechanical load and has been shown to produce cytokines. This study aims to assess the involvement of the IPFP in the progression of post-traumatic osteoarthritis (OA) through investigating the crosstalk between the IPFP and injured cartilage in vitro. METHODS: A single blunt impact (36 MPa) on healthy bovine articular cartilage explants was used to generate traumatized cartilage...
January 2017: Osteoarthritis and Cartilage
P Fiorino, A L V Américo, C R Muller, F S Evangelista, F Santos, A P O Leite, V Farah
AIMS: This study sought to investigate the metabolic, hemodynamic and autonomic responses in adult rats exposed to high-fat diet since post-weaning. MAIN METHODS: Young male Wistar rats were assigned into groups fed with standard normal diet (3% lipids; ND, n=8) or high-fat diet (30% lipids; HD, n=8) during 8weeks. Body composition, food intake, serum triglycerides, total cholesterol, insulin, leptin and adiponectin concentrations were determined. Hemodynamic and autonomic evaluations were performed...
September 1, 2016: Life Sciences
Richard B Allan, Simon V Vun, J Ian Spark
This study compared flow-mediated dilatation (FMD), peripheral artery tonometry (PAT), and serum nitric oxide (NO) measures of endothelial function in patients with peripheral artery disease (PAD) against age/gender matched controls. 25 patients (mean age: 72.4 years, M : F 18 : 7) with established PAD and an age/gender matched group of 25 healthy controls (mean age: 72.4 years, M : F 18 : 7) were studied. Endothelial function was measured using the % FMD, reactive hyperemia index (RHI) using PAT and serum NO (μmol)...
2016: International Journal of Vascular Medicine
Jaya Shukla, Amit Kumar Dinda, Abhay Krishna Srivastava, Kamna Srivastava, Bhagwant Rai Mittal, Guru Pad Bandopadhyaya
Tamoxifen is the most prescribed anticancer oral drug for increasing overall survival and decreasing recurrence and the risk of contralateral disease. However, some side effects, such as endometrial and liver tumors, thromboembolic disorders, and drug resistance, are associated with long-term tamoxifen treatment. We assessed the hematologic and organ toxicity after oral administration of three different doses of nanotamoxifen formulations. We also performed biodistribution studies of Technetium-99m ((99m)Tc)-nanotamoxifen after intravenous administration...
January 2016: World Journal of Nuclear Medicine
Yoko Sotoda, Shigeki Hirooka, Hiroyuki Orita, Ichiro Wakabayashi
Peripheral arterial disease (PAD) is an atherosclerotic obstructive disease of the arteries in lower extremities. Patients with PAD show high rates of mortality from coronary artery disease (CAD) and stroke. Smoking as well as diabetes is an important risk factor for PAD. A lesion of PAD in the lower extremities tends to be more proximal in smokers than in nonsmokers and to be more distal in patients with diabetes than in nondiabetics. By a systematic review, the odds ratio for PAD of smokers vs nonsmokers has been reported to be in the range of 1...
2015: Nihon Eiseigaku Zasshi. Japanese Journal of Hygiene
Federico Biscetti, Gianfranco Ferraccioli, Andrea Flex
Cilostazol (CIL) is effective for the treatment of patients with peripheral arterial disease (PAD). CIL is an orally administered drug with multiple effects, including anti-platelets aggregation, favorable functions on plasmatic lipids and vasodilator ones, but how these effects might be related to improvement in patients walking affected by PAD is not fully understood. The latest data demonstrate that nitric oxide (NO) is induced by CIL through endothelial nitric oxide synthase (eNOS) activation via a cyclic-AMP (cAMP)/ protein kinase A (PKA)- and PI3K/Akt- dependent mechanism...
2015: Current Vascular Pharmacology
Yasumasa Ikeda, Hirofumi Hamano, Akiho Satoh, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Ken-Ichi Aihara, Koichiro Tsuchiya, Toshiaki Tamaki
Low serum bilirubin levels are associated with the risk of cardiovascular diseases including peripheral artery disease. Bilirubin is known to exert its property such as antioxidant effect or the enhancement of flow-mediated vasodilation, however, bilirubin action on angiogenesis remains unclear. To investigate the molecular mechanism of bilirubin on angiogenic effect, we first employed C57BL/6J mice with unilateral hindlimb ischemia surgery and divided the mice into two groups (vehicle-treated group and bilirubin-treated group)...
November 2015: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Jessica Y Schneider, Sabine Rothmann, Frank Schröder, Jennifer Langen, Thomas Lücke, François Mariotti, Jean François Huneau, Jürgen C Frölich, Dimitrios Tsikas
Despite saturation of nitric oxide (NO) synthase (NOS) by its substrate L-arginine (Arg), oral and intravenous supplementation of Arg may enhance NO synthesis, a phenomenon known as "The L-arginine paradox". Yet, Arg is not only a source of NO, but is also a source for guanidine-methylated (N (G)) arginine derivatives which are all inhibitors of NOS activity. Therefore, Arg supplementation may not always result in enhanced NO synthesis. Concomitant synthesis of N (G)-monomethyl arginine (MMA), N (G),N (G)-dimethylarginine (asymmetric dimethylarginine, ADMA) and N (G),N (G´)-dimethylarginine (symmetric dimethylarginine, SDMA) from supplemented Arg may outweigh and even outbalance the positive effects of Arg on NO...
September 2015: Amino Acids
Arslan Arinc Kayacelebi, Jennifer Langen, Katharina Weigt-Usinger, Kristine Chobanyan-Jürgens, François Mariotti, Jessica Y Schneider, Sabine Rothmann, Jürgen C Frölich, Dorothee Atzler, Chi-Un Choe, Edzard Schwedhelm, Jean François Huneau, Thomas Lücke, Dimitrios Tsikas
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthesis, whereas L-arginine (Arg) and L-homoarginine (hArg) serve as substrates for NO synthesis. ADMA and other methylated arginines are generally believed to exclusively derive from guanidine (N (G))-methylated arginine residues in proteins by protein arginine methyltransferases (PRMTs) that use S-adenosylmethionine (SAM) as the methyl donor. L-Lysine is known for decades as a precursor for hArg, but only recent studies indicate that arginine:glycine amidinotransferase (AGAT) is responsible for the synthesis of hArg...
September 2015: Amino Acids
Gang Li, Jiyi Xia, Peng Jia, Jian Zhao, Yuqin Sun, Changxue Wu, Bin Liu
This study aims to estimate plasma levels of acylated ghrelin in children with pulmonary hypertension (PH) associated with congenital heart disease (CHD) and to correlate the levels of acylated ghrelin with endothelin-1 (ET-1), nitric oxide (NO), and clinical hemodynamic parameters. We investigated the plasma concentration of acylated ghrelin, ET-1, NO, and the hemodynamic parameters in 20 children with CHD, 20 children with PH-CHD, and 20 normal children. Plasma-acylated ghrelin and NO levels were significantly higher in CHD group than in control subjects (P < 0...
October 2015: Pediatric Cardiology
Xun Qi, Yonghui Yuan, Ke Xu, Hongshan Zhong, Zhen Zhang, Huan Zhai, Gefei Guan, Guibo Yu
BACKGROUND: Peripheral artery disease (PAD), which is caused by atherosclerosis, results in progressive narrowing and occlusion of the peripheral arteries and inhibits blood flow to the lower extremities. Therapeutic angiogenesis is a promising strategy for treating ischemia caused by PAD. Nitric oxide (NO) has been shown to be a key mediator of angiogenesis. It has been demonstrated that β-cyclodextrincan stimulate vessel growth in rabbit corneas. In this study, we assessed the mechanism of action and therapeutic potential of a new angiogenic molecule, (2-hydroxypropyl)-β-cyclodextrin (2HP-β-CD)...
2015: PloS One
Byung-Ryul Cho, Dong Ryeol Ryu, Kwang-Soon Lee, Dong-Keon Lee, Soochan Bae, Dong Goo Kang, Qingen Ke, Sylvia S Singh, Kwon-Soo Ha, Young-Guen Kwon, Dongwon Lee, Peter M Kang, Young-Myeong Kim
Therapeutic angiogenesis has achieved promising results for ischemic diseases or peripheral artery disease in preclinical and early-phase clinical studies. We examined the therapeutic angiogenic effects of HPOX, which is biodegradable polymer composing the antioxidant p-hydroxybenzyl alcohol (HBA), in a mouse model of hindlimb ischemia. HPOX effectively stimulated blood flow recovery, compared with its degraded compounds HBA and 1,4-cyclohexendimethanol, via promotion of capillary vessel density in the ischemic hindlimb...
2015: Biomaterials
Aleksandra Staniszewska, Sriram Rajagopalan, Abdullah Al-Shaheen, Frank Thies, Julie Brittenden
OBJECTIVE: Recent interest has focused on the role of the methyl-arginines, endogenous inhibitors of nitric oxide, as adverse prognostic indicators. To date, few studies have assessed the role of symmetric dimethyl-arginine (SDMA) in patients with peripheral arterial disease. We aimed to determine the relationship, if any, of SDMA to all-cause mortality and disease severity as assessed by the ankle-brachial index (ABI) in patients with symptomatic peripheral arterial disease (PAD). METHODS: In 238 patients with symptomatic PAD and an ABI of <0...
May 2015: Journal of Vascular Surgery
Lena Vogl, Johannes Pohlhammer, Andreas Meinitzer, Barbara Rantner, Marietta Stadler, Slobodan Peric, Angelika Hammerer-Lercher, Peter Klein-Weigel, Gustav Fraedrich, Florian Kronenberg, Barbara Kollerits
BACKGROUND: High serum concentrations of l-arginine and l-homoarginine increase nitric oxide (NO) availability and thereby improve endothelial function. Information about the association of these markers with peripheral arterial disease (PAD) and related outcomes is sparse. METHODS: l-arginine, its metabolites and l-homoarginine were analyzed in the CAVASIC Study including 232 male patients diagnosed with intermittent claudication and 246 age- and diabetes-matched controls...
April 2015: Atherosclerosis
Shuhua Chen, Jie Yang, Hong Xiang, Wei Chen, Hua Zhong, Guoping Yang, Ting Fang, Hao Deng, Hong Yuan, Alex F Chen, Hongwei Lu
The hyperglycemia-induced production of oxidative stress results in endothelial cell dysfunction. Previous studies have demonstrated that sphingosine-1-phosphate (S1P) regulates an array of biological activities in endothelial cells mediated by sphingosine-1-phosphate receptors (S1PRs). However, the role of S1PR-mediated signaling pathways in hyperglycemia-induced endothelial cell dysfunction is currently unknown. In the present study, we aimed to explore the role of S1PRs in endothelial cell dysfunction. For this purpose, hyperglycemia-induced oxidative stress was examined using human umbilical vein endothelial cells (HUVECs) cultured with either normal (5...
April 2015: International Journal of Molecular Medicine
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