Flow, NO, and atherogenesis

Cooke, John P.

doi:10.1073/pnas.0430082100

Cited by 127 publications

(99 citation statements)

References 38 publications

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“…With respect to vascular reactivity and structure, NO plays a dominant role as a vasodilation factor that also potently inhibits vascular smooth muscle proliferation, leukocyte infi ltration, and platelet adherence and aggregation [ 25 ]. Furthermore, NO is a powerful agonist of EC proliferation and migration.…”

Section: Discussionmentioning

confidence: 99%

Role of Nitric Oxide Signaling in Endothelial Differentiation of Embryonic Stem Cells

Huang

Fleißner

Sun

et al. 2010

Stem Cells and Development

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Signaling pathways that govern embryonic stem cell (ESCs) differentiation are not well characterized. Nitric oxide (NO) is a potent vasodilator that modulates other signaling pathways in part by activating soluble guanylyl cyclase (sGC) to produce cyclic guanosine monophosphate (cGMP). Because of its importance in endothelial cell (EC) growth in the adult, we hypothesized that NO may play a critical role in EC development. Accordingly, we assessed the role of NO in ESC differentiation into ECs. Murine ESCs differentiated in the presence of NO synthase (NOS) inhibitor NG-nitroarginine methyl ester ( l -NAME) for up to 11 days were not signifi cantly different from vehicle-treated cells in EC markers. However, by 14 days, l -NAME-treated cells manifested modest reduction in EC markers CD144, FLK1, and endothelial NOS. ESC-derived ECs generated in the presence of l -NAME exhibited reduced tube-like formation in Matrigel. To understand the discrepancy between early and late effects of l -NAME, we assessed the NOS machinery and observed low mRNA expression of NOS and sGC subunits in ESCs, compared to differentiating cells after 14 days. In response to NO donors or activation of NOS or sGC, cellular cGMP levels were undetectable in undifferentiated ESCs, at low levels on day 7, and robustly increased in day 14 cells. Production of cGMP upon NOS activation at day 14 was inhibited by l -NAME, confi rming endogenous NO dependence. Our data suggest that NOS elements are present in ESCs but inactive until later stages of differentiation, during which period NOS inhibition reduces expression of EC markers and impairs angiogenic function.

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Section: Discussionmentioning

confidence: 99%

Role of Nitric Oxide Signaling in Endothelial Differentiation of Embryonic Stem Cells

Huang

Fleißner

Sun

et al. 2010

Stem Cells and Development

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“…Atherosclerotic lesions preferentially develop in areas of the vasculature that are exposed to non-laminar blood flow, whereas laminar flow is atheroprotective [6].…”

Section: Introductionmentioning

confidence: 99%

“…NQO1 detoxifies quinines and their derivatives and prevents their participation in redox cycling, therefore reducing oxidative stress [3]. NQO1 also protects cells from oxidative stress by maintaining antioxidant forms of ubiquinone and vitamin E. Furthermore, recent reports show that highly expressed and inducible endogenous NQO1 in cardiovascular cells may act as a potential superoxide scavenger [4,5].Atherosclerotic lesions preferentially develop in areas of the vasculature that are exposed to non-laminar blood flow, whereas laminar flow is atheroprotective [6].Exposure of endothelial cells to laminar flow activates antioxidant response element (ARE)-driven transcriptional activity and increases the expression of a set of ARE-regulated genes, including NQO1, HO-1 (heme oxygenase-1) and GST (glutathione S-transferase) [7]. These findings suggest that NQO1 is an important enzyme in protecting vessels against oxidative stress and atherogenesis.…”

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confidence: 99%

The C609T variant of NQO1 is associated with carotid artery plaques in patients with type 2 diabetes

Han

Kang

Kim

et al. 2009

Molecular Genetics and Metabolism

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“…•-) generation and a decrease in nitric oxide (NO) are observed [4]. This is of major importance since an overproduction of O 2…”

Section: Introductionmentioning

confidence: 99%

Resveratrol disrupts peroxynitrite-triggered mitochondrial apoptotic pathway: a role for Bcl-2

et al. 2008

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Resveratrol (3,4 0 ,5-trihydroxystilbene) is a phytochemical believed to be partly responsible for the cardioprotective effects of red wine due to its numerous biological activities. Here, we studied biochemical pathways underlying peroxynitrite-mediated apoptosis in endothelial cells and potential mechanisms responsible for resveratrol cytoprotective action. Peroxynitrite triggered endothelial cell apoptosis through caspases-8, -9 and -3 activation implying both mitochondrial and death receptor apoptotic pathways. Resveratrol was able to prevent peroxynitrite-induced caspases-3 and -9 activation, but not caspase-8 activation. Additionally, peroxynitrite increased intracellular levels of Bax without affecting those of Bcl-2, increasing consequently the Bax/Bcl-2 ratio. This ratio decreased when cells where pre-incubated with 10 and 50 lM resveratrol, mainly due to resveratrol ability per se to increase Bcl-2 intracellular levels without affecting Bax intracellular levels. These results propose an additional mechanism whereby resveratrol may exert its cardioprotective effects and suggest a key role for Bcl-2 in the resveratrol anti-apoptotic action, especially in disrupting peroxynitrite-triggered mitochondrial pathway.

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Flow, NO, and atherogenesis

Abstract: CorrectionsPHARMACOLOGY. For the article ''Beneficial effects of antioxidants and L-arginine on oxidation-sensitive gene expression and endothelial NO synthase activity at sites of disturbed shear stress,''

Cited by 127 publications

References 38 publications

Role of Nitric Oxide Signaling in Endothelial Differentiation of Embryonic Stem Cells

Role of Nitric Oxide Signaling in Endothelial Differentiation of Embryonic Stem Cells

The C609T variant of NQO1 is associated with carotid artery plaques in patients with type 2 diabetes

Resveratrol disrupts peroxynitrite-triggered mitochondrial apoptotic pathway: a role for Bcl-2

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