Can ADMA play a role in determining pulmonary hypertension related to chronic obstructive pulmonary disease?

Telo, Selda; Kırkıl, Gamze; Kuluöztürk, Mutlu; Balın, Mehmet; Deveci, Figen

doi:10.1111/crj.12675

Cited by 21 publications

(18 citation statements)

References 29 publications

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“…65 In patients with chronic obstructive pulmonary disease, ADMA may help in the determination of the presence of PH. 63 In patients with CTEPH, elevated ADMA levels were associated with mean right atrial pressure, cardiac index, and mixed venous oxygen saturation. 62 Zhang et al observed similar tendency in their study, wherein patients with both CTEPH and PAH had significantly higher ADMA levels than the control group.…”

Section: Asymmetric Dimethylargininementioning

confidence: 94%

Circulating biomarkers in chronic thromboembolic pulmonary hypertension

Zhang

Pang

et al. 2019

Pulm. circ.

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Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious condition characterized with chronic organized thrombi that obstruct the pulmonary vessels, leading to pulmonary hypertension (PH) and ultimately right heart failure. Although CTEPH is the only form of PH that can be cured with surgical intervention, not all patients with CTEPH will be deemed operable. Some CTEPH patients still have a poor prognosis. Therefore, the determination of diagnostic and prognostic biomarkers of CTEPH is of great importance for the early intervention to improve prognosis of patients with CTEPH. Several markers related to multiple mechanisms of CTEPH have been recently identified as circulating diagnostic and prognostic biomarkers in these patients. However, the existing literature review of biomarkers of CTEPH is relatively sparse. In this article, we review recent advances in circulating biomarkers of CTEPH and describe future applications of these biomarkers in the management of CTEPH.

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Section: Asymmetric Dimethylargininementioning

confidence: 94%

Circulating biomarkers in chronic thromboembolic pulmonary hypertension

Zhang

Pang

et al. 2019

Pulm. circ.

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“…In another study, Telo et al. 20 compared patients with chronic-obstructive lung disease (COPD) who had developed PAH (defined as systolic PAP (sPAP) > 35mm Hg) to COPD patients without elevated sPAP and to healthy controls. They found a significantly elevated mean ADMA concentration in COPD patients with PAH as compared to both other groups.…”

Section: Adma Is Increased In Hypoxia and In Pah: Observational Humanmentioning

confidence: 99%

Metabolism of asymmetric dimethylarginine in hypoxia: from bench to bedside

et al. 2020

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Acute hypoxia and chronic hypoxia induce pulmonary vasoconstriction. While hypoxic pulmonary vasoconstriction is a physiological response if parts of the lung are affected, global exposure to hypoxic conditions may lead to clinical conditions like high-altitude pulmonary hypertension. Nitric oxide is the major vasodilator released from the vascular endothelium. Nitric oxide-dependent vasodilation is impaired in hypoxic conditions. Inhibition of nitric oxide synthesis is the most rapid and easily reversible molecular mechanism to regulate nitric oxide-dependent vascular function in response to physiological and pathophysiological stimuli. Asymmetric dimethylarginine is an endogenous, competitive inhibitor of nitric oxide synthase and a risk marker for major cardiovascular events and mortality. Elevated asymmetric dimethylarginine has been observed in animal models of hypoxia as well as in human cohorts under chronic and chronic intermittent hypoxia at high altitude. In lowlanders, asymmetric dimethylarginine is high in patients with pulmonary hypertension. We have recently shown that high asymmetric dimethylarginine at sea level is a predictor for high-altitude pulmonary hypertension. Asymmetric dimethylarginine is a highly regulated molecule, both by its biosynthesis and metabolism. Methylation of L-arginine by protein arginine methyltransferases was shown to be increased in hypoxia. Furthermore, the metabolism of asymmetric dimethylarginine by dimethylarginine dimethylaminohydrolases (DDAH1 and DDAH2) is decreased in animal models of hypoxia. Whether these changes are caused by transcriptional or posttranslational modifications remains to be elucidated. Current data suggest a major role of asymmetric dimethylarginine in regulating pulmonary arterial nitric oxide production in hypoxia. Further studies are needed to decipher the molecular mechanisms regulating asymmetric dimethylarginine in hypoxia and to understand their clinical significance.

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“…The scenario is further acerbated by the significantly reduced plasma arginine concentrations in patients with renal failure in comparison to healthy patients [95]. Of pathophysiological significance, elevated circulating plasma concentrations of ADMA provide a marker of risk for a wide range of endothelial dysfunction and renal and cardiovascular disorders, such as renal failure, chronic obstructive pulmonary disease (COPD) such as pulmonary arterial hypertension [97], pulmonary fibrosis, rheumatoid arthritis (RA) [98], increased cardiovascular morbidity and mortality, diabetes, heart failure, and elevated systemic blood pressure [54,99,100]. High plasma ADMA was correlated with high all-cause mortality and late mortality in renal transplant recipients.…”

Section: Adma—the Small Molecule Metabolite Product Of Arginine Mementioning

confidence: 99%

The Biological Axis of Protein Arginine Methylation and Asymmetric Dimethylarginine

Fulton

Brown

Zheng

2019

IJMS

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Protein post-translational modifications (PTMs) in eukaryotic cells play important roles in the regulation of functionalities of the proteome and in the tempo-spatial control of cellular processes. Most PTMs enact their regulatory functions by affecting the biochemical properties of substrate proteins such as altering structural conformation, protein–protein interaction, and protein–nucleic acid interaction. Amid various PTMs, arginine methylation is widespread in all eukaryotic organisms, from yeasts to humans. Arginine methylation in many situations can drastically or subtly affect the interactions of substrate proteins with their partnering proteins or nucleic acids, thus impacting major cellular programs. Recently, arginine methylation has become an important regulator of the formation of membrane-less organelles inside cells, a phenomenon of liquid–liquid phase separation (LLPS), through altering π-cation interactions. Another unique feature of arginine methylation lies in its impact on cellular physiology through its downstream amino acid product, asymmetric dimethylarginine (ADMA). Accumulation of ADMA in cells and in the circulating bloodstream is connected with endothelial dysfunction and a variety of syndromes of cardiovascular diseases. Herein, we review the current knowledge and understanding of protein arginine methylation in regards to its canonical function in direct protein regulation, as well as the biological axis of protein arginine methylation and ADMA biology.

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Can ADMA play a role in determining pulmonary hypertension related to chronic obstructive pulmonary disease?

Cited by 21 publications

References 29 publications

Circulating biomarkers in chronic thromboembolic pulmonary hypertension

Circulating biomarkers in chronic thromboembolic pulmonary hypertension

Metabolism of asymmetric dimethylarginine in hypoxia: from bench to bedside

The Biological Axis of Protein Arginine Methylation and Asymmetric Dimethylarginine

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