Nitric Oxide Synthase Type III

Publication Title: 
Aging

Excessive production of reactive oxygen species (ROS) contributes to progression of atherosclerosis, at least in part by causing endothelial dysfunction and inflammatory activation. The class III histone deacetylase SIRT1 has been implicated in extension of lifespan. In the vasculature,SIRT1 gain-of-function using SIRT1 overexpression or activation has been shown to improve endothelial function in mice and rats via stimulation of endothelial nitric oxide (NO) synthase (eNOS). However, the effects of SIRT1 loss-of-function on the endothelium in atherosclerosis remain to be characterized.

Author(s): 
Stein, Sokrates
Sch‰fer, Nicola
Breitenstein, Alexander
Besler, Christian
Winnik, Stephan
Lohmann, Christine
Heinrich, Kathrin
Brokopp, Chad E.
Handschin, Christoph
Landmesser, Ulf
Tanner, Felix C.
L¸scher, Thomas F.
Matter, Christian M.
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Insulin-like growth factor 1 (IGF-1) stimulates cell proliferation and is crucial for maintenance of somatic tissues. However, this effect is associated with the inhibition of FOXO transcription factors and downregulation of antioxidative enzymes. In this study, we compared the responses of primary dermal fibroblasts and human umbilical vein endothelial cells with IGF-1 treatment. We found that IGF-1 primarily downregulated enzymatic antioxidants in skin fibroblasts. However, human umbilical vein endothelial cells were protected from an IGF-1-mediated decrease in antioxidative capacity.

Author(s): 
Stone, Rivka C.
Kim, Soyeon
Barnes, Betsy J.
Aviv, Abraham
Publication Title: 
Biogerontology

Nitric oxide (NO) triggers multiple signal transduction pathways and contributes to the control of numerous cellular functions. Previous studies have shown in model organisms that the alteration of NO production has important effects on aging and lifespan. We studied in a large sample (763 subjects, age range 19-107†years) the variability of the three human genes (NOS1, -2, -3) coding for the three isoforms of the NADPH-dependent enzymes named NO synthases (NOS) which are responsible of NO synthesis.

Author(s): 
Montesanto, Alberto
Crocco, Paolina
Tallaro, Federica
Pisani, Francesca
Mazzei, Bruno
Mari, Vincenzo
Corsonello, Andrea
Lattanzio, Fabrizia
Passarino, Giuseppe
Rose, Giuseppina
Publication Title: 
Current Opinion in Clinical Nutrition and Metabolic Care

PURPOSE OF REVIEW: The purpose of this review is to highlight recent publications examining nitric oxide production in health and disease and its association with clinical nutrition and alterations in metabolism. RECENT FINDINGS: The role of the cofactor tetrahydrobiopterin in nitric oxide production and its relation with arginine availability is indicated as an important explanation for the arginine paradox. This offers potential for nitric oxide regulation by dietary factors such as arginine or its precursors and vitamin C.

Author(s): 
Luiking, Yvette C.
Engelen, MariÎlle P. K. J.
Deutz, Nicolaas E. P.
Publication Title: 
The Journal of Clinical Investigation

Children conceived by assisted reproductive technologies (ART) display a level of vascular dysfunction similar to that seen in children of mothers with preeclamspia. The long-term consequences of ART-associated vascular disorders are unknown and difficult to investigate in healthy children. Here, we found that vasculature from mice generated by ART display endothelial dysfunction and increased stiffness, which translated into arterial hypertension in vivo. Progeny of male ART mice also exhibited vascular dysfunction, suggesting underlying epigenetic modifications.

Author(s): 
Rexhaj, Emrush
Paoloni-Giacobino, Ariane
Rimoldi, Stefano F.
Fuster, Daniel G.
Anderegg, Manuel
Somm, Emmanuel
Bouillet, Elisa
Allemann, Yves
Sartori, Claudio
Scherrer, Urs
Publication Title: 
PloS One

Microglial activation plays an important role in neuroinflammation, which contributes to neuronal damage, and inhibition of microglial activation may have therapeutic benefits that could alleviate the progression of neurodegeneration. Recent studies have indicated that the antimalarial agent artemisinin has the ability to inhibit NF-?B activation. In this study, the inhibitory effects of artemisinin on the production of proinflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated primary microglia.

Author(s): 
Zhu, Cansheng
Xiong, Zhaojun
Chen, Xiaohong
Peng, Fuhua
Hu, Xueqiang
Chen, Yanming
Wang, Qing
Publication Title: 
Circulation

BACKGROUND: C-reactive protein (CRP), the prototypic marker of inflammation, has been shown to be an independent predictor of cardiovascular events. Endothelial nitric oxide synthase (eNOS) deficiency is a pivotal event in atherogenesis. METHODS AND RESULTS: We tested the effect of CRP on eNOS expression and bioactivity in cultured human aortic endothelial cells (HAECs). CRP decreased eNOS mRNA, protein abundance, and enzyme activity in HAECs. Furthermore, eNOS bioactivity assayed by cyclic GMP levels was significantly reduced by CRP.

Author(s): 
Venugopal, Senthil Kumar
Devaraj, Sridevi
Yuhanna, Ivan
Shaul, Philip
Jialal, Ishwarlal
Publication Title: 
American Journal of Physiology. Heart and Circulatory Physiology

We hypothesized that elevated partial pressures of O(2) would increase perivascular nitric oxide (*NO) synthesis. Rodents with O(2)- and.NO-specific microelectrodes implanted adjacent to the abdominal aorta were exposed to O(2) at partial pressures from 0.2 to 2.8 atmospheres absolute (ATA). Exposures to 2.0 and 2.8 ATA O(2) stimulated neuronal (type I) NO synthase (nNOS) and significantly increased steady-state.NO concentration, but the mechanism for enzyme activation differed at each partial pressure.

Author(s): 
Thom, Stephen R.
Fisher, Donald
Zhang, Jie
Bhopale, Veena M.
Ohnishi, S. Tsuyoshi
Kotake, Yashige
Ohnishi, Tomoko
Buerk, Donald G.
Publication Title: 
Arteriosclerosis, Thrombosis, and Vascular Biology

OBJECTIVE: In addition to being a cardiovascular risk marker, recent studies support a role for CRP in atherothrombosis. Several investigators have reported that CRP binds to Fcgamma receptors on leukocytes. The aim of the study is to determine the processing of CRP by human aortic endothelial cells (HAECs). METHODS AND RESULTS: Binding studies were performed by incubation of HAECs with biotinylated CRP (B-CRP, 25 to 200 microg/mL) for 30 to 180 minutes at 4 degrees C. B-CRP binding was quantitated using streptavidin-fluorescein isothiocyanate followed by flow cytometry.

Author(s): 
Devaraj, Sridevi
Du Clos, Terry W.
Jialal, Ishwarlal
Publication Title: 
Journal of Vascular Surgery

BACKGROUND: Defensins are cysteine-rich cationic polypeptides released from neutrophils that exhibit powerful antimicrobial activities. Because inflammation, including neutrophil infiltration and release of defensins, may play an important role in atherosclerosis and other vascular diseases, we determined whether alpha-defensin could cause endothelial dysfunction, a major initial event of atherosclerosis, in porcine coronary arteries. METHODS: Porcine coronary arteries were sliced into 5-mm rings and treated with different concentrations of human recombinant alpha-defensin for 24 hours.

Author(s): 
Kougias, Panagiotis
Chai, Hong
Lin, Peter H.
Yao, Qizhi
Lumsden, Alan B.
Chen, Changyi

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