Effects of Nitric Oxide on Atherosclerosis

Pong, Terrence; Huang, Paul L.

doi:10.1002/9781118828533.ch28

Cited by 4 publications

(3 citation statements)

References 55 publications

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“…The mechanisms impairing eNOS activity in disease are multiple, including inhibition by oxidised low-density lipoprotein [33,75] and lysophosphatidylcholine [76], as well as endogenous NOS inhibitors, such as asymmetric dimethylarginine (ADMA) [21,77]. In addition to the inhibition of eNOS-derived NO, the uncoupling of eNOS from its cofactor or substrate leads to production of ROS, further contributing to endothelial dysfunction [78]. nNOS has been shown to be protective against endothelial dysfunction and atherosclerosis, with studies demonstrating the development of accelerated atherosclerosis in nNOS knockout mice [79,80].…”

Section: Endothelial Dysfunctionmentioning

confidence: 99%

Dysfunctional and Dysregulated Nitric Oxide Synthases in Cardiovascular Disease: Mechanisms and Therapeutic Potential

Roy,

Wilcox,

Webb

et al. 2023

IJMS

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Nitric oxide (NO) plays an important and diverse signalling role in the cardiovascular system, contributing to the regulation of vascular tone, endothelial function, myocardial function, haemostasis, and thrombosis, amongst many other roles. NO is synthesised through the nitric oxide synthase (NOS)-dependent L-arginine-NO pathway, as well as the nitrate-nitrite-NO pathway. The three isoforms of NOS, namely neuronal (NOS1), inducible (NOS2), and endothelial (NOS3), have different localisation and functions in the human body, and are consequently thought to have differing pathophysiological roles. Furthermore, as we continue to develop a deepened understanding of the different roles of NOS isoforms in disease, the possibility of therapeutically modulating NOS activity has emerged. Indeed, impaired (or dysfunctional), as well as overactive (or dysregulated) NOS activity are attractive therapeutic targets in cardiovascular disease. This review aims to describe recent advances in elucidating the physiological role of NOS isoforms within the cardiovascular system, as well as mechanisms of dysfunctional and dysregulated NOS in cardiovascular disease. We then discuss the modulation of NO and NOS activity as a target in the development of novel cardiovascular therapeutics.

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Section: Endothelial Dysfunctionmentioning

confidence: 99%

Dysfunctional and Dysregulated Nitric Oxide Synthases in Cardiovascular Disease: Mechanisms and Therapeutic Potential

Roy,

Wilcox,

Webb

et al. 2023

IJMS

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“…The effector molecules downstream of NO include ion channels found in the membrane, enzymes, and several key proteins in the mitochondria, cytosol and nuclear compartment ( Villanueva & Giulivi, 2010 ; Zhang, 2017 ). All three NOS isoforms are abundant in the heart and in atherosclerotic plaques ( Pong & Huang, 2015 ; Wilcox et al, 1997 ) and have addressed the expression of NOS isoforms in normal and during the progression of atherosclerotic lesions. NOS3 found in quiescent blood vessels is expressed by ECs, where it maintains basal physiological functions.…”

Section: Survey Methodologymentioning

confidence: 99%

The expanding roles of neuronal nitric oxide synthase (NOS1)

Solanki

Rajpoot

Bezsonov

et al. 2022

PeerJ

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The nitric oxide synthases (NOS; EC 1.14.13.39) use L-arginine as a substrate to produce nitric oxide (NO) as a by-product in the tissue microenvironment. NOS1 represents the predominant NO-producing enzyme highly enriched in the brain and known to mediate multiple functions, ranging from learning and memory development to maintaining synaptic plasticity and neuronal development, Alzheimer’s disease (AD), psychiatric disorders and behavioral deficits. However, accumulating evidence indicate both canonical and non-canonical roles of NOS1-derived NO in several other tissues and chronic diseases. A better understanding of NOS1-derived NO signaling, and identification and characterization of NO-metabolites in non-neuronal tissues could become useful in diagnosis and prognosis of diseases associated with NOS1 expression. Continued investigation on the roles of NOS1, therefore, will synthesize new knowledge and aid in the discovery of small molecules which could be used to titrate the activities of NOS1-derived NO signaling and NO-metabolites. Here, we address the significance of NOS1 and its byproduct NO in modifying pathophysiological events, which could be beneficial in understanding both the disease mechanisms and therapeutics.

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“…So BH2 is competitively replaced with eNOS-bound BH4 and this form of eNOS synthesizes superoxide instead of NO [53]. Also, L-arginine is converted to superoxide instead, and its conversion subsequently causes LDL oxidation and endothelial dysfunction [35,[54][55][56]. Finally, atherosclerotic plaque formation and thrombosis occur in the late stage of atherosclerosis [52].…”

Section: Atherosclerosis and Nitric Oxidementioning

confidence: 99%

Mechanisms of Medicinal Plant Activity on Nitric Oxide (NO) Bioavailability as Prospective Treatments for Atherosclerosis

Malekmohammad

Sewell

Rafieian-Kopaei

2020

CPD

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Background and objective: Atherosclerosis is one of the leading causes of human morbidity globally and reduced bioavailability of vascular nitric oxide (NO) has a critical role in the progression and development of the atherosclerotic disease. Loss of NO bioavailability, for example via a deficiency of the substrate (L-arginine) or cofactors for endothelial nitric oxide synthase (eNOS), invariably leads to detrimental vascular effects such as impaired endothelial function and increased smooth muscle cell proliferation, deficiency of the substrate (Larginine) or cofactors for eNOS. Various medicinal plants and their bioactive compounds or secondary metabolites with fewer side effects are potentially implicated in preventing cardiovascular disease by increasing NO bioavailability, thereby ameliorating endothelial dysfunction. In this review, we describe the most notable medicinal plants and their bioactive compounds that may be appropriate for enhancing NO bioavailability, and treatment of atherosclerosis. Methods: The material in this article was obtained from noteworthy scientific databases, including Web of Science, PubMed, Science Direct, Scopus and Google Scholar. Results: Medicinal plants and their bioactive compounds influence NO production through diverse mechanisms including the activation of the nuclear factor kappa B (NF-κB) signaling pathway, activating protein kinase C (PKC)-α, stimulating protein tyrosine kinase (PTK), reducing the conversion of nitrite to NO via nitrate-nitrite reduction pathways, induction of eNOS, activating the phosphatidylinositol 3-kinase (PI3K)/serine threonine protein kinase B (AKT) (PI3K/AKT/eNOS/NO) pathway and decreasing oxidative stress. Conclusion: Medicinal plants and/or their constituent bioactive compounds may be considered as safe therapeutic options for enhancing NO bioavailability and prospective preventative therapy for atherosclerosis.

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Effects of Nitric Oxide on Atherosclerosis

Cited by 4 publications

References 55 publications

Dysfunctional and Dysregulated Nitric Oxide Synthases in Cardiovascular Disease: Mechanisms and Therapeutic Potential

Dysfunctional and Dysregulated Nitric Oxide Synthases in Cardiovascular Disease: Mechanisms and Therapeutic Potential

The expanding roles of neuronal nitric oxide synthase (NOS1)

Mechanisms of Medicinal Plant Activity on Nitric Oxide (NO) Bioavailability as Prospective Treatments for Atherosclerosis

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