L-Arginine-Nitric Oxide-Asymmetric Dimethylarginine Pathway and the Coronary Circulation: Translation of Basic Science Results to Clinical Practice

Cziráki, Attila; Lenkey, Zsófia; Sulyok, E.; Szokodi, István; Koller, Ákos

doi:10.3389/fphar.2020.569914

Cited by 37 publications

(18 citation statements)

References 168 publications

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“…NO, known as the “endothelium‐derived relaxing factor,” is a bioactive product of endothelial NO synthase (eNOS) and biosynthesized from L‐arginine, oxygen, and NADPH, which regulates many endothelial cell functions. It contributes to vessel regulation of the cardiovascular system by signaling the surrounding smooth muscle to relax, inhibiting the proliferation of VSMCs, and preventing platelet aggregation 14–16 . Growing evidence has shown that ADMA, an endogenous competitive inhibitor of NO synthase, plays a critical role during the process of endothelial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Effect of profilin‐1 on the asymmetric dimethylarginine‐induced vascular lesion‐associated hypertension

Cheng²,

et al. 2021

The Kaohsiung J of Med Scie

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Previous studies have demonstrated that the levels of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthesis, are strongly associated with hypertension, diabetes, and cardiovascular diseases. Profilin‐1, an actin‐binding protein, has been documented to be involved in endothelial injury and in the proliferation of vascular smooth muscle cells resulting from hypertension. However, the role of profilin‐1 in ADMA‐induced vascular injury in hypertension remains largely unknown. Forty healthy subjects and forty‐two matched patients with essential hypertension were enrolled, and the related indexes of vascular injury in plasma were detected. Rat aortic smooth muscle cells (RASMCs) were treated with different concentrations of ADMA for different periods of time and transfected with profilin‐1 small hairpin RNA to interrupt the expression of profilin‐1. To determine the role of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, RASMCs were pretreated with AG490 or rapamycin. The expression of profilin‐1 was tested using real‐time polymerase chain reaction (PCR) and western blot analysis. Cell proliferation was measured by flow cytometry and 3‐(4,5‐dimethylthiazol‐2yl)‐2,5‐diphenyltetrazoliumbromide assays. Compared with healthy subjects, the levels of ADMA and profilin‐1 were markedly elevated in hypertensive individuals, while the levels of NO were significantly decreased (p < 0.05). In vitro, studies showed ADMA‐induced profilin‐1 expression in a concentration‐ and time‐dependent manner in RASMCs (p < 0.05), concomitantly with promoting the proliferation of RASMCs. Furthermore, ADMA‐mediated proliferation of RASMCs and upregulation expression of profilin‐1 were inhibited by blockade of the JAK2/STAT3 pathway or knockdown of profilin‐1. Profilin‐1 implicated in the ADMA‐mediated vascular lesions in hypertension.

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Section: Discussionmentioning

confidence: 99%

Effect of profilin‐1 on the asymmetric dimethylarginine‐induced vascular lesion‐associated hypertension

Cheng²,

et al. 2021

The Kaohsiung J of Med Scie

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“…Another potential target to attenuate vascular ageing is the arginine (Arg) metabolic pathway. Being the substrate for nitric oxide synthase (NOS), Arg has important nitric oxide (NO) dependent vasodilatory and antithrombotic effects but also several NO independent effects that help to maintain and improve vascular health [ 170 ]. For these reasons, it has become a popular dietary supplement, although the CV benefits from long-term supplementation remain questionable.…”

Section: ‘Arteriometabolomics’ Approachmentioning

confidence: 99%

Metabolomics of Arterial Stiffness

Paapstel

Kals

2022

Metabolites

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Arterial stiffness (AS) is one of the earliest detectable signs of structural and functional alterations of the vessel wall and an independent predictor of cardiovascular events and death. The emerging field of metabolomics can be utilized to detect a wide spectrum of intermediates and products of metabolism in body fluids that can be involved in the pathogenesis of AS. Research over the past decade has reinforced this idea by linking AS to circulating acylcarnitines, glycerophospholipids, sphingolipids, and amino acids, among other metabolite species. Some of these metabolites influence AS through traditional cardiovascular risk factors (e.g., high blood pressure, high blood cholesterol, diabetes, smoking), while others seem to act independently through both known and unknown pathophysiological mechanisms. We propose the term ‘arteriometabolomics’ to indicate the research that applies metabolomics methods to study AS. The ‘arteriometabolomics’ approach has the potential to allow more personalized cardiovascular risk stratification, disease monitoring, and treatment selection. One of its major goals is to uncover the causal metabolic pathways of AS. Such pathways could represent valuable treatment targets in vascular ageing.

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“…14 Although it has been less studied than VSA, its prevalence is almost equal as identified by Ong et al 10 Several pathogenic hypotheses exist, all of them placing endothelial dysfunction at the core. It is known that endothelial dysfunction is associated with cardiovascular risk factors, 15 as well as with serum concentrations of asymmetrical dimethylarginine (an inhibitor of nitric oxide synthase) 16 and decreased shear stress. 17 State-of-the-art treatments for coronary vasomotor disorders focus on the use of calcium channel blockers to induce smooth muscle relaxation, but the association of endothelial dysfunction with modifiable risk factors may be a potential target for lifestyle changes and pharmacotherapy, specifically directed to improve the function of the vascular endothelium.…”

Section: Evaluation Of Coronary Vasomotor Disordersmentioning

confidence: 99%

Invasive evaluation of coronary microvascular dysfunction

Travieso

Jerónimo-Baza

Faria

et al. 2022

Journal of Nuclear Cardiology

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Coronary microvascular dysfunction (CMD) is a prevalent cause of ischemic heart disease and is associated with poorer quality of life and worse patient outcomes. Both functional and structural abnormalities of the microcirculation can generate ischemia in the absence of epicardial stenosis or worsen concomitant obstructive coronary artery disease (CAD). The invasive assessment of CMD allows for the evaluation of the entirety of the coronary vascular tree, from the large epicardial vessels to the microcirculation, and enables the study of vasomotor function through vasoreactivity testing. The standard evaluation of CMD includes vasomotor assessment with acetylcholine, as well as flow- and resistance-derived indices calculated with either thermodilution or Doppler guidewires. Tailored treatment based upon the information gathered from the invasive evaluation of CMD has been demonstrated to reduce the burden of angina; therefore, a thorough understanding of these procedures is warranted with the aim of improving the quality of life of the patient. This review summarizes the most widespread approaches for the invasive evaluation of CMD, with a focus on patients with ischemia and non-obstructive CAD.

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L-Arginine-Nitric Oxide-Asymmetric Dimethylarginine Pathway and the Coronary Circulation: Translation of Basic Science Results to Clinical Practice

Cited by 37 publications

References 168 publications

Effect of profilin‐1 on the asymmetric dimethylarginine‐induced vascular lesion‐associated hypertension

Effect of profilin‐1 on the asymmetric dimethylarginine‐induced vascular lesion‐associated hypertension

Metabolomics of Arterial Stiffness

Invasive evaluation of coronary microvascular dysfunction

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