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      Urinary orosomucoid: a new marker of cardiovascular risk in psoriatic patients?

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          Abstract

          Purpose

          Psoriasis is one of the most common lifelong lasting dermatologic diseases. According to the latest studies, psoriatic patients have a higher risk of developing cardiovascular diseases. Psoriasis is considered as a systemic inflammatory disease. Several oxidative stress markers have been shown to be elevated in psoriasis. However, a panel of biomarkers has not been used yet. This study was aimed at exploring the connection between a panel of biomarkers (C-reactive protein, asymmetric dimethylarginine, uric acid, total antioxidant capacity, malondialdehyde, and orosomucoid [ORM]) and cardiovascular risk in psoriatic patients.

          Patients and methods

          The inclusion criterion was the onset of psoriasis with skin lesions. Exclusion criteria were impaired renal function (eGFR<60 mL/min/1.73 m 2), acute inflammations (urinary, respiratory, skin inflammation, etc), autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosus, or inflammatory bowel disease), and any kind of biological antipsoriatic treatment. Patients with a medical history of myocardial infarction, coronary heart disease, stroke, transient ischemic attack, and carotid artery stenosis were also excluded. Biomarkers were measured by routine procedures, ELISA and HPLC. QRISK®2-2017 was used to assess 10-year risk of cardiovascular disease development. Psoriasis severity was measured by the Psoriasis Area and Severity Index.

          Results

          One hundred and fourteen psoriatic patients were enrolled. Only urinary orosomucoid and urinary orosomucoid/urinary creatinine (u-ORM/u-CREAT) ratio showed significant correlation with QRISK score (u-ORM, r=0.245; u-ORM/u-CREAT, r=0.309). When comparing mild psoriatic patients to moderate psoriatic patients, significant differences could only be found in u-ORM and u-ORM/u-CREAT ratio.

          Conclusion

          There seems to be a connection between urinary ORM and cardiovascular risk. U-ORM and u-ORM/u-CREAT ratio could be used as an indicator of low-grade inflammation in mild and moderate psoriasis. However, it is the 10-year follow-up of cardiovascular events that will determine the usefulness of this biomarker panel.

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          Most cited references 43

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          Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis.

          During primate evolution, a major factor in lengthening life-span and decreasing age-specific cancer rates may have been improved protective mechanisms against oxygen radicals. We propose that one of these protective systems is plasma uric acid, the level of which increased markedly during primate evolution as a consequence of a series of mutations. Uric acid is a powerful antioxidant and is a scavenger of singlet oxygen and radicals. We show that, at physiological concentrations, urate reduces the oxo-heme oxidant formed by peroxide reaction with hemoglobin, protects erythrocyte ghosts against lipid peroxidation, and protects erythrocytes from peroxidative damage leading to lysis. Urate is about as effective an antioxidant as ascorbate in these experiments. Urate is much more easily oxidized than deoxynucleosides by singlet oxygen and is destroyed by hydroxyl radicals at a comparable rate. The plasma urate levels in humans (about 300 microM) is considerably higher than the ascorbate level, making it one of the major antioxidants in humans. Previous work on urate reported in the literature supports our experiments and interpretations, although the findings were not discussed in a physiological context.
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            Pathogenesis and clinical features of psoriasis.

            Psoriasis, a papulosquamous skin disease, was originally thought of as a disorder primarily of epidermal keratinocytes, but is now recognised as one of the commonest immune-mediated disorders. Tumour necrosis factor alpha, dendritic cells, and T-cells all contribute substantially to its pathogenesis. In early-onset psoriasis (beginning before age 40 years), carriage of HLA-Cw6 and environmental triggers, such as beta-haemolytic streptococcal infections, are major determinants of disease expression. Moreover, at least nine chromosomal psoriasis susceptibility loci have been identified. Several clinical phenotypes of psoriasis are recognised, with chronic plaque (psoriasis vulgaris) accounting for 90% of cases. Comorbidities of psoriasis are attracting interest, and include impairment of quality of life and associated depressive illness, cardiovascular disease, and a seronegative arthritis known as psoriatic arthritis. A more complete understanding of underlying pathomechanisms is leading to new treatments, which will be discussed in the second part of this Series.
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              Alpha-1-acid glycoprotein.

              Alpha-1-acid glycoprotein (AGP) or orosomucoid (ORM) is a 41-43-kDa glycoprotein with a pI of 2.8-3.8. The peptide moiety is a single chain of 183 amino acids (human) or 187 amino acids (rat) with two and one disulfide bridges in humans and rats,respectively. The carbohydrate content represents 45% of the molecular weight attached in the form of five to six highly sialylated complex-type-N-linked glycans. AGP is one of the major acute phase proteins in humans, rats, mice and other species. As most acute phase proteins, its serum concentration increases in response to systemic tissue injury, inflammation or infection, and these changes in serum protein concentrations have been correlated with increases in hepatic synthesis. Expression of the AGP gene is controlled by a combination of the major regulatory mediators, i.e. glucocorticoids and a cytokine network involving mainly interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF alpha), interleukin-6 and IL-6 related cytokines. It is now well established that the acute phase response may take place in extra-hepatic cell types, and may be regulated by inflammatory mediators as observed in hepatocytes. The biological function of AGP remains unknown; however,a number of activities of possible physiological significance, such as various immunomodulating effects, have been described. AGP also has the ability to bind and to carry numerous basic and neutral lipophilic drugs from endogenous (steroid hormones) and exogenous origin; one to seven binding sites have been described. AGP can also bind acidic drugs such as phenobarbital. The immunomodulatory as well as the binding activities of AGP have been shown to be mostly dependent on carbohydrate composition. Finally, the use of AGP transgenic animals enabled to address in vivo, functionality of responsive elements and tissue specificity, as well as the effects of drugs that bind to AGP and will be an useful tool to determine the physiological role of AGP.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                TCRM
                tcriskman
                Therapeutics and Clinical Risk Management
                Dove
                1176-6336
                1178-203X
                05 July 2019
                2019
                : 15
                : 831-837
                Affiliations
                [1 ] Dermatology Unit, Zsigmondy Vilmos SPA Hospital , Harkány, Hungary
                [2 ] Department of Public Health Medicine, Medical School, University of Pécs , Pécs, Hungary
                [3 ] Department of Laboratory Medicine, Medical School, University of Pécs , Pécs, Hungary
                [4 ] János Szentágothai Research Centre, University of Pécs , Pécs, Hungary
                [5 ] Heart Institute, Medical School, University of Pécs , Pécs, Hungary
                Author notes
                Correspondence: Balázs Németh Department of Public Health Medicine, Medical School, University of Pécs , Szigeti Street 12, H-7624, Pécs, HungaryTel +36 7 253 6394Fax +36 72536 395 Email balazs.nemeth@ 123456aok.pte.hu
                Article
                197633
                10.2147/TCRM.S197633
                6616299
                © 2019 Németh et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Tables: 3, References: 47, Pages: 7
                Categories
                Original Research

                Medicine

                psoriasis, orosomucoid, oxidative stress, c-reactive protein, biomarker, cardiovascular risk

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