Relationship Between Ubiquitin-Specific Peptidase 18 and Hypertension in Polish Adult Male Subjects: A Cross-Sectional Pilot Study

Dziamałek-Macioszczyk, Paulina; Harazny, Joanna; Kwella, Norbert; Wojtacha, Paweł; Jung, Susanne; Dienemann, Thomas; Schmieder, Roland E.; Stompór, Tomasz

doi:10.12659/msm.921919

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…In our earlier work, we assessed sUSP18 in men with AHT yet naïve to treatment and those without AHT, and we confirmed the role of this protein as an indicator of an enhanced afterload. Based on the observation that systolic-diastolic hypertensive (otherwise healthy) subjects were characterized by significantly higher median sUSP18 values than other groups (diastolic hypertensive group and healthy individuals), we hypothesized that high serum USP18 concentrations may correspond with a counterregulatory process aiming to compensate for cardiomyocyte contractile function and stabilize their structure [18]. In our current study, healthy individuals in G1 (using no medications, never diagnosed with AHT, cardiovascular, or any other chronic disease) and KTx patients in G5 (with treated AHT and excellent graft function) were characterized with the highest sUSP18 concentrations, with median values of 1143 pg/mL and 853.6 pg/mL, respectively (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-Specific Protease 18 in Chronic Kidney Disease—Another Emerging Biomarker to Consider?

Dziamałek-Macioszczyk,

Winiarska,

Pawłowska

et al. 2024

Biomedicines

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Ubiquitin-specific protease 18 (USP18) is a protein recognized for its dual enzymatic and non-enzymatic nature. It is involved in many physiological processes like the cell cycle and cell signaling. It also suppresses heart muscle remodeling upon an increase in the afterload. The role of USP18 in kidney pathology remains unknown. The objective of the study was to assess the relationship between serum and urine USP18 levels, the factors contributing to cardiovascular risk, and the markers of kidney disease activity at different stages of chronic kidney disease (CKD). One hundred participants, aged between 24 and 85 years (mean 53.1 ± 17.1 years), were included. Five groups (n = 20 each) were recruited according to their renal status (healthy individuals, patients with proteinuric glomerulonephritis, patients with non-proteinuric CKD, patients who were treated with hemodialysis, and kidney transplant recipients). The measurements of serum and urine USP18 levels were performed using ELISA. The median serum USP18 level was the highest in healthy participants (1143.0 pg/mL) and kidney transplant recipients (856.6 pg/mL), whereas, in individuals with different forms of CKD, it fitted within the range of 402.1–471.9 pg/mL. Urinary USP18 reached the highest level in the group of CKD patients not yet on dialysis (303.3 pg/mL). Only in this group did it correlate with serum creatinine and urea concentrations. Our results suggest the inhibition of cardioprotective USP18 signaling when kidney function is impaired. Moreover, an increased level of urinary USP18 may indicate chronic tubular damage.

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Section: Discussionmentioning

confidence: 99%

Ubiquitin-Specific Protease 18 in Chronic Kidney Disease—Another Emerging Biomarker to Consider?

Dziamałek-Macioszczyk,

Winiarska,

Pawłowska

et al. 2024

Biomedicines

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“…USP18 has been reported to inhibit cardiac remodeling and prevent the development of heart failure through the TAK1-p38/JNK1/2 signaling pathway [21]. In addition, the serum USP18 levels were found to be signi cantly increased in the male hypertensive patients, suggesting the important role of USP18 in the development of cardiovascular disease [22]. An et al examined the mRNA levels of ABCG1 using real-time polymerase chain reaction(RT-qPCR) in hepatocyte-speci c USP18 transgenic (USP18-HTG) mice fed by high-fat diet (HFD), and the results showed that ABCG1 mRNA levels were signi cantly increased in USP18-HTG mice compared to controls.…”

Section: Introductionmentioning

confidence: 98%

Investigating the potential role of USP18 in atherosclerosis based on bioinformatics analysis

Zhang

Liu

et al. 2023

Preprint

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Background: Ubiquitin-specific protease 18 (USP18), is a member of the ubiquitin-specific protease family. Previous studies have shown that USP18 expression is upregulated in the patients with heart failure and USP18 is considered as a novel target for the treatment of heart failure. However, the role of USP18 in atherosclerosis remains unclear. In this study, we aimed to investigate the expression pattern of USP18 in atherosclerosis and its relationship between the extent of atherosclerotic and the cholesterol transporter protein ABCG1. Methods: GSE6054 dataset was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed by using the "limma" package in R (version 4.1.3). H-DOCK was applied to perform protein-protein docking for predicting the interaction between USP18 and ATP-binding cassette transporter protein G1 (ABCG1). Immunohistochemistry(IHC), immunofluorescence(IF), and Western blot were used to assess the protein expression of USP18 and ABCG1 in human coronary arteries. Dual immunofluorescencewas performed for co-localization analysis of USP18 and ABCG1 Results: Bioinformatics analysis identified 462 DEGs including 239 upregulated and 223 downregulated genes in familial hypercholesterolaemia (FH) patients, of which USP18 was upregulated in monocytes. Gene Ontology enrichment analysis indicated that the biological functions of USP18 were mainly enriched in endopeptidase activity and cytokine-mediated signaling. Protein-protein docking by H-DOCK showed that USP18 and ABCG1 interacted at a free energy of -20 kcal/mol (free energy < 0 was considered meaningful). USP18 expression is upregulated in patients with coronary artery disease and negatively correlates with the extent of atherosclerosis. At the same time, The expression of ABCG1 is downregulated in CHD and SCD patients and is more pronounced in SCD patients. In atherosclerotic tissues, USP18 and ABCG1 expression were positively correlated. In addition, double immunofluorescence assay showed co-localization of USP18 and ABCG1. Conclusions: USP18 is a differentially expressed gene of FH, and its expression in atherosclerosis is closely related to the extent of atherosclerosis.

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“…USP18 has been reported to inhibit cardiac remodeling and prevent the development of heart failure through the TAK1-p38/JNK1/2 signaling pathway [20]. In addition, the serum USP18 levels were found to be signi cantly increased in the male hypertensive patients, suggesting the important role of USP18 in the development of cardiovascular disease [21]. An et al examined the mRNA levels of ABCG1 using real-time polymerase chain reaction(RT-qPCR) in hepatocyte-speci c USP18 transgenic (USP18-HTG) mice fed by high-fat diet (HFD), and the results showed that ABCG1 mRNA levels were signi cantly increased in USP18-HTG mice compared to controls.…”

Section: Introductionmentioning

confidence: 98%

Investigating the potential role of USP18 in atherosclerosis by regulating cholesterol efflux based on bioinformatics analysis

Zhang

Liu

et al. 2022

Preprint

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Background Ubiquitin-specific protease 18 (USP18), also known as UBP43, is a member of the ubiquitin-specific protease family involved in suppressing viral activity and promoting tumor migration. Previous studies have shown that USP18 expression is upregulated in the patients with heart failure and USP18 is considered as a novel target for the treatment of heart failure. However, the role of USP18 in atherosclerosis remains unclear. In this study, we sought to explore the role of USP18 on ATP-binding cassette transporter protein G1 (ABCG1)-dependent cholesterol efflux. Methods GSE6054 dataset was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed by using the "limma" package in R (version 4.1.3). H-DOCK was applied to perform protein-protein docking for predicting the interaction between USP18 and ABCG1. Immunohistochemistry(IHC), immunofluorescence(IF), and Western blot were used to assess the protein expression of USP18 and ABCG1 in human coronary arteries. Dual immunofluorescence was performed for co-localization analysis of USP18 and ABCG1 Results Bioinformatics analysis identified 462 differentially expressed genes including 239 upregulated and 223 downregulated genes in familial hypercholesterolaemia (FH) patients, of which USP18 was upregulated in monocytes. Gene Ontology enrichment analysis indicated that the biological functions of USP18 were mainly enriched in endopeptidase activity and cytokine-mediated signaling. Protein-protein docking by H-DOCK showed that USP18 and ABCG1 interacted at a free energy of -20 kcal/mol (free energy < 0 was considered meaningful). IHC, IF and Western blot analyses revealed an increased expression level of USP18 in coronary arteries from patients with coronary atherosclerotic heart disease (CHD) , but Western blot analyses revealed a decreased expression level of USP18 in coronary arteries from patients with sudden cardiac death (SCD) compared with controls. At the same time, ABCG1 expression was decreased in coronary arteries from both CHD and SCD patients with a higher significance in SCD patients. In addition, double immunofluorescence assay showed no significant co-localization of USP18 and ABCG1. Conclusions USP18 may contribute to the development of atherogenesis through regulating ABCG1-dependent cholesterol efflux from macrophages.

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Relationship Between Ubiquitin-Specific Peptidase 18 and Hypertension in Polish Adult Male Subjects: A Cross-Sectional Pilot Study

Cited by 4 publications

References 33 publications

Ubiquitin-Specific Protease 18 in Chronic Kidney Disease—Another Emerging Biomarker to Consider?

Ubiquitin-Specific Protease 18 in Chronic Kidney Disease—Another Emerging Biomarker to Consider?

Investigating the potential role of USP18 in atherosclerosis based on bioinformatics analysis

Investigating the potential role of USP18 in atherosclerosis by regulating cholesterol efflux based on bioinformatics analysis

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