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Relationship Between Plasma Osteopontin and Arginine Pathway Metabolites in Patients With Overt Coronary Artery Disease.

ABSTRACT: Introduction:Osteopontin (OPN) is involved in ectopic calcification. Its circulating form is upregulated in coronary artery disease (CAD) patients. Circulating OPN levels positively correlate with oxidative stress, one of the major triggers of endothelial dysfunction. Endothelial dysfunction is, in turn, associated with reduced nitric oxide (NO) bioavailability due to the impaired arginine pathway. The aim of this study was to better understand the correlations between OPN, oxidative stress markers, and the arginine pathway metabolites. Methods and Results:ELISA and mass spectrometry techniques have been used to evaluate circulating OPN and arginine pathway/oxidative stress metabolites, respectively, in twenty-five control subjects and thirty-three patients with overt atherosclerosis. OPN positively correlates with 2,3-dinor-8isoPGF2a levels (p = 0.02), ornithine (p = 0.01), ADMA (p = 0.001), SDMA (p = 0.03), and citrulline (p = 0.008) levels only in CAD patients. In addition, citrulline positively correlated with ADMA (p = 0.02) levels, possibly as result of other sources of citrulline biosynthetic pathways. Conclusion:The association between OPN and impaired arginine/NO pathway could play a role in the inhibition of endothelial NO synthase (eNOS) and/or in the arginase activation in the context of CAD patients. However, further studies are needed to verify the cause-effect relationship between OPN, oxidative stress, and arginine/NO pathway dysregulation.

SUBMITTER: Moschetta D

PROVIDER: S-EPMC7424048 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Relationship Between Plasma Osteopontin and Arginine Pathway Metabolites in Patients With Overt Coronary Artery Disease.

Moschetta Donato D Di Minno Matteo Nicola Dario MND Porro Benedetta B Perrucci Gianluca L GL Valerio Vincenza V Alfieri Valentina V Massaiu Ilaria I Orekhov Alexander N AN Di Minno Alessandro A Songia Paola P Cavalca Viviana V Myasoedova Veronika A VA Poggio Paolo P

Frontiers in physiology 20200806

<h4>Introduction</h4>Osteopontin (OPN) is involved in ectopic calcification. Its circulating form is upregulated in coronary artery disease (CAD) patients. Circulating OPN levels positively correlate with oxidative stress, one of the major triggers of endothelial dysfunction. Endothelial dysfunction is, in turn, associated with reduced nitric oxide (NO) bioavailability due to the impaired arginine pathway. The aim of this study was to better understand the correlations between OPN, oxidative str ...[more]

PMID: 32848891

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Project description:Study Objectives: Coronary artery disease is considered to be the major cause of death amongst patients with ischemic stroke. The coronary artery calcium (CAC) score is related not only to sleep-disordered breathing, but also with future risk of cardiovascular mortality. We investigated the association between the severity of sleep-disordered breathing and CAC score in patients with ischemic stroke. Methods: We included 32 patients who underwent coronary multichannel computed tomography and polysomnography (within 2 years of the stroke event) amongst the patients admitted to our clinic due to acute ischemic stroke. We investigated vascular risk factors, polysomnography findings, and sleep questionnaire scores, and their relationships with the CAC score. Results: All patients were found to have sleep apnea of any degree, and 23 (72%) had severe sleep apnea. Twenty-three (72%) patients had a positive CAC score. Higher CAC scores were associated with elevated respiratory disturbance index (RDI), apnea index, oxygen desaturation index, and STOP-BANG test scores. Multivariate analysis after adjusting for potential confounding factors revealed independent relationships between the CAC score and the RDI (ß [SE] = 5.3 [2.1], p = 0.01), oxygen desaturation index (ß [SE] = 6.8 [2.8], p = 0.02), and STOP-BANG test score (ß [SE] = 90.3 [37.7], p = 0.02). Conclusion: Our findings indicate a relationship between coronary atherosclerotic burden measured by the CAC score and the severity of sleep apnea. Performing polysomnography could be useful for investigating the severity of hidden coronary artery disease among these patients.Brief summaryCurrent Knowledge/Study Rationale: The effect of sleep apnea on coronary artery disease in patients with ischemic stroke has not been explored. We investigated the relationship between sleep apnea, its related characteristics and the coronary artery calcium score in patients with stroke.Study Impact: Our findings reveal a close relationship between the atherosclerosis-related burden measured by the coronary artery calcium score and the severity of sleep apnea that persisted after adjusting for confounding variables related to the risk of coronary artery disease. Proper detection and treatment of sleep apnea might mitigate the risk of future coronary events in patients with ischemic stroke.

Dataset Information

Relationship Between Plasma Osteopontin and Arginine Pathway Metabolites in Patients With Overt Coronary Artery Disease.

Publications

Relationship Between Plasma Osteopontin and Arginine Pathway Metabolites in Patients With Overt Coronary Artery Disease.

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