Plasma levels of matrix metalloproteinase-2 and -9 in male and female patients with cirrhosis of different aetiologies

Huang, Chih Yang; Tseng, Kuo‐Chih; Lin, Ming-Nan; Tsai, Jen Pi; Su, Cheng

doi:10.1136/jclinpath-2015-202932

Cited by 6 publications

(8 citation statements)

References 38 publications

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“…However, the increased levels of MMP-9 have been described in several pathologic conditions and/or inflammatory status suggesting that it is not clearly specific in cancer [ 4 ]. Accordingly, several inflam-matory cytokines and growth factors that in turn may activate the Activator Protein-1/A Polyoma Enhancer Binding Protein-3 factor (AP-1/PEA3) and NF-kB led MMP-9 overexpression [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

MMP-9 overexpression is associated with intragenic hypermethylation of MMP9 gene in melanoma

Falzone

Salemi

Travali

et al. 2016

Aging

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Tumor spreading is associated with the degradation of extracellular matrix proteins, mediated by the overexpression of matrix metalloproteinase 9 (MMP-9). Although, such overexpression was linked to epigenetic promoter methylation, the role of intragenic methylation was not clarified yet. Melanoma was used as tumor model to investigate the relationship between the DNA intragenic methylation of MMP9 gene and MMP-9 overexpression at transcriptional and protein levels. Computational analysis revealed DNA hypermethylation within the intragenic CpG-2 region of MMP9 gene in melanoma samples with high MMP-9 transcript levels. In vitro validation showed that CpG-2 hotspot region was hypermethylated in the A375 melanoma cell line with highest mRNA and protein levels of MMP-9, while low methylation levels were observed in the MEWO cell line where MMP-9 was undetectable. Concordant results were demonstrated in both A2058 and M14 cell lines. This correlation may give further insights on the role of MMP-9 upregulation in melanoma.

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Section: Introductionmentioning

confidence: 99%

MMP-9 overexpression is associated with intragenic hypermethylation of MMP9 gene in melanoma

Falzone

Salemi

Travali

et al. 2016

Aging

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“…In previous studies, these markers were elevated in patients with cirrhosis. 43 – 50 CD62L is a cell adhesion protein, MMP-2 is an enzyme involved in the degradation of extracellular matrix proteins, while TNF-α is a proinflammatory cytokine. 43 – 49 TNF-α induces the expression of MMP-2, and MMPs increase the activity of TNF-α.…”

Section: Discussionmentioning

confidence: 99%

“… 46 MMP-2 seems elevated in cirrhosis (increasing in line with Child-Pugh class) and during HSC activation and after partial hepatectomy, while CD62L is increased in patients with acute decompensation and positively correlates with MELD scores. 46 , 48 – 50 The knowledge of TNF-α is more established, which increases early in chronic liver diseases and correlates with the disease stage. 51 , 52 TNF-α is also involved in the development and progression of cirrhosis, and it continues to be produced in established cirrhosis, and further increases in decompensation and ACLF.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin for patients with cirrhosis. A randomized, placebo-controlled trial

Kronborg,

Schierwagen,

Trošt

et al. 2023

Hepatology Communications

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Background: Patients with cirrhosis and portal hypertension face a high risk of complications. Besides their anti-inflammatory and antifibrotic effects, statins may reduce portal pressure and thus the risk of complications and mortality. We aimed to investigate the effects of atorvastatin on hospital admissions, mortality, inflammation, and lipidomics in cirrhosis with portal hypertension. Methods: We performed a double-blinded, randomized, placebo-controlled clinical trial among patients with cirrhosis and portal hypertension. Atorvastatin (10–20 mg/d) was administered for 6 months. We measured splanchnic hemodynamics, analyzed inflammatory markers, and performed lipidomics at baseline and after 6 months. Results: Seventy-eight patients were randomized, with 38 patients allocated to atorvastatin and 40 patients to placebo. Fifty-nine patients completed 6 months of intervention. Comparisons between changes in each group were calculated. Liver-related complications and mortality were similar between the groups. The HVPG and Model for End-stage Liver Disease score did not change between groups (p=0.95 and 0.87, respectively). Atorvastatin decreased 3 of 42 inflammatory markers, CD62-L-selectin, matrix metalloproteinases-2, and TNF-α (p-values: 0.005, 0.011, and 0.023, respectively), while lipidomics was not significantly changed. Conclusions: In patients with cirrhosis, atorvastatin was safe to use, but did not reduce mortality, the risk of liver-related complications, or the HVPG. Atorvastatin induced minor anti-inflammatory effects and minor effects on lipids during a 6-month treatment period.

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“…В ряде работ отмечено увеличение содержания в крови ТИМП-1, -2, ММП-2, -8, -9, -13 при циррозе печени [11][12][13][14][15][16][17], в том числе в печеночной крови [11], хотя имеются данные о снижении активности ММП-9 [13] или об отсутствии различий в активности ММП-1 в зависимости от наличия или отсутствия цирроза [16]. Снижение экспрессии ММП может быть связано с дефицитом цинка, уменьшением количества клеток-продуцентов (гепатоцитов), гиперактивностью звездчатых клеток, экспрессирующих ТИМП-1 [18].…”

Section: медицинский вестник северного кавказаunclassified

Complications of liver cirrhosis and matrix metalloproteinases: clinical relationships

Dudov,

Koroy,

Yagoda

2023

Medical news of the North Caucasus

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Ставропольский государственный медицинский университет, Российская Федерация complicaTions of liVer cirrhosis anD maTrix meTalloproTeinases: clinical relaTionshipsDudov T. r., Koroy p. V., Yagoda a. V. stavropol state medical university, russian federation В исследовании проводилось изучение взаимосвязи матриксных металлопротеиназ (ММП) и их тканевых ингибиторов (ТИМП) с особенностями течения цирроза печени (ЦП). Обследовано 159 больных (53 женщины, 106 мужчин) в возрасте от 26 до 64 лет. Контрольную группу составили 72 практически здоровых человека. Определяли содержание в крови ТИМП-1, ММП-1, ММП-9, рассчитывали соотношение ТИМП-1/ММП-1, ТИМП-1/ММП-9. При ЦП наблюдалось увеличение концентрации ММП-1 и ТИМП-1 в крови, соотношения ТИМП-1/ММП-9 и снижение величин ММП-9, ТИМП-1/ММП-1. Прогностически неблагоприятные варианты заболевания (классы В/С по Child-Pugh, значения шкалы MELD≥9 баллов, суб-и декомпенсированная портальная гипертензия, наличие асцита или печеночной энцефалопатии) характеризовались более высоким содержанием ТИМП-1, ММП-1, ММП-9 в крови и более низкими значениями ТИМП-1/ММП-1, ТИМП-1/ММП-9. У больных ЦП с предшествующим кровотечением из вен пищевода регистрировались более высокая концентрация ММП-1 в крови и более низкие величины ТИМП-1/ММП-1. Рост сывороточных уровней матриксных металлопротеиназ, сопряженный с проявлениями портальной гипертензии, свидетельствует об их роли в формировании осложнений заболевания. Ключевые слова: цирроз печени, осложнения, матриксные металлопротеиназы, тканевые ингибиторы матриксных металлопротеиназThe paper presents the resaults of study is to study the relationship of the matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) with the features of the course of liver cirrhosis (LC). 159 patients with LC (53 women, 106 men) aged from 26 to 64 years were examined. The control group consisted of 72 practically healthy people. The blood content of TIMP-1, MMP-1 and MMP-9 was determined; the ratio of TIMP-1/MMP-1, TIMP-1/MMP-9 was calculated. There was an increase in the concentration of MMP-1 and TIMP-1 in the blood, the ratio of TIMP-1/MMP-9 and a decrease in the values of MMP-9, TIMP-1/MMP-1 in LC. Prognostically unfavorable variants of the disease (Child-Pugh B/C classes, values of MELD scale ≥9 points, sub-and decompensated portal hypertension, the presence of ascites or hepatic encephalopathy) were characterized by a higher content of TIMP-1, MMP-1, MMP-9 in the blood and lower values of TIMP-1/MMP-1, TIMP-1/MMP-9. In patients with LC with previous bleeding from the esophageal varices, a higher concentration of MMP-1 in the blood and lower values of TIMP-1/MMP-1 were recorded. Thus, the increase in serum levels of matrix metalloproteinases associated with the manifestations of portal hypertension indicates their role in the formation of complications of the disease.

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Plasma levels of matrix metalloproteinase-2 and -9 in male and female patients with cirrhosis of different aetiologies

Abstract: Plasma MMP-2 level may be a useful diagnostic marker for monitoring hepatic fibrogenesis in patients with disease of different aetiologies.

Cited by 6 publications

References 38 publications

MMP-9 overexpression is associated with intragenic hypermethylation of MMP9 gene in melanoma

MMP-9 overexpression is associated with intragenic hypermethylation of MMP9 gene in melanoma

Atorvastatin for patients with cirrhosis. A randomized, placebo-controlled trial

Complications of liver cirrhosis and matrix metalloproteinases: clinical relationships

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