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Vascular Endothelial Dysfunction and Atherosclerosis: Role of Nitric Oxide System

  • Chapter
Pathophysiology and Pharmacotherapy of Cardiovascular Disease

Abstract

Nitric oxide (NO) is a vasoprotective molecule that plays a critical role in modulating endothelial functions. A compromised NO bioavailability due to defective NO generation by endothelial nitric oxide synthase (eNOS) has been suggested as one of the mechanisms leading to the pathogenesis of vascular abnormalities such as atherosclerosis. NO synthesis requires L-arginine as a substrate for eNOS as well as several cofactors for its catalytic activity. Vascular endothelial dysfunction and atherosclerosis are associated with deficiencies in the levels of arginine and eNOS cofactor tetrahydrobiopterin (BH4). Reactive oxygen species (ROS), aberrant lipid metabolism and elevated protein kinase C have also been reported to alter NO biosynthesis by modulating eNOS activity. In vitro studies as well as use of animal models of vascular diseases have provided some evidence regarding the molecular mechanisms of the reduced NO bioavailability associated with atherosclerosis. This chapter briefly summarises key studies highlighting the role of interplay between pro-atherogenic factors such as ROS, growth factors and vasoactive peptides and NO system in vascular endothelial dysfunction and atherosclerosis.

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Acknowledgements

The work in the author’s laboratory is supported by funding from the Canadian Institutes of Health Research (CIHR) operating grant number 67037 to AKS. ERSC was a recipient of a studentship from the Faculty of Graduate and Postdoctoral Studies of the University of Montreal.

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Authors and Affiliations

  1. Laboratory of Cell Signaling, Research Center of the University of Montreal Hospital Center Department of Nutrition, University of Montreal, Montreal, QC, Canada

    Estelle R. Simo Cheyou

  2. Laboratory of Cell Signaling, Research Center of the University of Montreal Hospital Center (CRCHUM)-Tour Viger, R08 430 – 900 St Denis Street, Montreal, H2X 0A9, QC, Canada

    Ashok K. Srivastava PhD

  3. Department of Nutrition and Medicine, University of Montreal, R08 430 – 900 St Denis Street, Montreal, Quebec, H2X 0A9, Canada

    Ashok K. Srivastava PhD

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  1. Estelle R. Simo Cheyou
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Correspondence to Ashok K. Srivastava PhD .

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  1. Center for Drug Evaluation and Research Division of Cardiovascular and Renal Products, US Food and Drug Administration, Silver Spring, Maryland, USA

    Gowraganahalli Jagadeesh

  2. Pharmacology Unit, AIMST University, Bedong, Malaysia

    Pitchai Balakumar

  3. Center for Drug Evaluation and Research Division of Cardiovascular and Renal Products, US Food and Drug Administration, Silver Spring, Maryland, USA

    Khin Maung-U

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Cheyou, E.R.S., Srivastava, A.K. (2015). Vascular Endothelial Dysfunction and Atherosclerosis: Role of Nitric Oxide System. In: Jagadeesh, G., Balakumar, P., Maung-U, K. (eds) Pathophysiology and Pharmacotherapy of Cardiovascular Disease. Adis, Cham. https://doi.org/10.1007/978-3-319-15961-4_26

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  • DOI: https://doi.org/10.1007/978-3-319-15961-4_26

  • Publisher Name: Adis, Cham

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