Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019270 (hernia)
 15,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although abnormal collagen metabolism has been ascribed an important role in the high recurrence rates after surgical hernia repair, knowledge on tissue sampled in the region affected by inguinal hernias is poor. In the present study, we determined collagen type I and type III in the skin of adult patients with indirect and direct inguinal hernias by both immunohistochemistry and Western blot analysis. In addition, we quantified the immunohistochemical expression of fibronectin and matrix metalloproteinase (MMP)-1 and -13. The results indicated that the ratio of collagen type I/III was significantly decreased in the skin of patients with either indirect (n = 9) or direct hernia (n = 7), with a concomitant increase in collagen type III (p < 0.001 vs. controls, n = 7, without affection of the inguinal region). There was no significant difference between patients with indirect and direct hernia (p > 0.05). MMP-13 was not expressed in any of the skin samples investigated, whereas MMP-1 was found in the epidermis. Fibronectin was predominantly detected at the epidermal-dermal junction. MMP-1, MMP-13 and fibronectin levels were significantly different between patients and controls (p > 0. 05). We conclude that in contrast to the unchanged expression of fibronectin and MMP-1 and MMP-13, the decreased ratios of collagen tpye I/III with the basically increased amount of collagen type III could be of significant importance for the pathophysiology of hernias. The specific ratio collagen I/III probably reflects the altered structural integrity and mechanical stability of the connective tissue in both indirect and direct hernias. Moreover, our findings stress that hernias should be regarded as the manifestation of a systemic disease in the inguinal region with a genetic background, explaining the high recurrence rates after repeated suture repair, as well as the usefulness of surgical meshes in this clinical setting.
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PMID:Expression of the extracellular matrix proteins collagen I, collagen III and fibronectin and matrix metalloproteinase-1 and -13 in the skin of patients with inguinal hernia. 1086 44

The late appearance ofincisional hernias several years after laparotomy and the high recurrence rates after operation strongly imply the presence of a disorder of the connective tissue, although a specific defect in patients with incisional hernias has not yet been identified. In the present study we used both immunohistochemistry and Western blot analysis to evaluate the ratio of collagen I and III and the expression of the metalloproteinases (MMP) 1 and 13 in the fascia of patients with incisional or recurrent incisional hernias. Samples of healthy skin or stable skin scar in patients without hernias served as controls. Altogether, our data indicated a significantly decreased ratio of collagen I/III in the fascia of patients with incisional hernias and recurrent incisional hernias. Furthermore, in these patients the expression of MMP-1 was decreased compared to the controls, whereas MMP-13 could not be detected in any fascia sample, with or without hernias present. For the first time, our results give evidence of the existence of a possible collagen disorder in these patients. The decreased ratio ofcollagen I/III is explainable due to a relative increase of collagen type III, which is known to be characterized by thin fibril diameters and lowered mechanical strength. The altered collagen ratio might be the result of the decreased activity of MMP-1, whereas the absent MMP-13 expression did not seem to modify the scar formation. Thus, our data indicate the presence of collagen metabolic disorders in patients with incisional hernias and recurrent incisional hernias. Furthermore, these results might explain the poor results of a mesh-free hernia repair, which again builds up scar tissue of inadequate collagen composition and strength.
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PMID:Collagen I/III and matrix metalloproteinases (MMP) 1 and 13 in the fascia of patients with incisional hernias. 1129 60

Since many years the importance of a weakness of the soft tissue for the development of hernias is discussed controversially. The tensile strength of the tissue is supposed to depend largely on the varying proportion of type I collagen with its high tensile strength and the immature type III collagen. Their relation is regulated by several collagenases, mainly matrix metalloproteinases-1 and -13 (MMP-1 and MMP-13), whereas fibronectin plays a key role for the adherence of cells within the extracellular matrix. The aim of this study was to investigate whether an alteration in type I and type III collagen synthesis, amounts of MMP-1 and MMP-13 and the expression of fibronectin were associated with the development of inguinal hernia. We analysed the hernial sac of patients with indirect (n = 9) and direct (n = 7) inguinal hernias and peritoneum in controls (n = 7) by immunohistochemistry and Western blot analysis. The results showed that the ratio of relative amount of I/III collagen was markedly decreased in patients with either indirect or direct hernias as compared with controls (p < 0.001) with a concomitant increase in type III collagen synthesis. MMP-13 was expressed neither in the hernial sac nor in the peritoneum of the controls, but the positive reactions of MMP-1 were found in the surface of the subserosa of the hernial sac in patients with indirect or direct hernias without any difference compared to controls. Furthermore, the relative amount of fibronectin in patients with either indirect or direct hernias is not significantly different from controls (p > 0.05). In regard to the known alterations of the collagen metabolism in fascia and skin of hernia patients the changed collagen I/III ratio with its increase of type III collagen in hernial sacs support the presence of a systemic disturbance of collagen metabolism. The absence of changes of the expression of collagenases (MMP-1, MMP-13) and the constant levels of fibronectin underline the central role of collagen synthesis for the development of indirect or direct hernias.
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PMID:Synthesis of type I and III collagen, expression of fibronectin and matrix metalloproteinases-1 and -13 in hernial sac of patients with inguinal hernia. 1134 10

The aim of this study was to investigate the collagen matrix in recurrent inguinal hernias. Total ribonucleic acid (RNA) was extracted from skin fibroblasts of three groups (control group I = healthy skin; control group II = plain skin scar; recurrent inguinal hernia group = skin of recurrent inguinal hernias; each n = 5). Reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis were used to investigate the expression of procollagen type I/- III, MMP-1, and MMP-13 mRNAs. Both ratios of procollagen types I to III mRNAs and collagen types I to III were apparently decreased in the recurrent hernia group compared to those of both control groups (p < 0.01). Significant differences were caused by the increase of both procollagen type III mRNA and collagen type III protein synthesis. A concomitant increase of MMP-1 and MMP-13 mRNAs and proteins was also observed in the recurrent hernia group and showed significant differences compared to those of both control groups I and II, respectively (p < 0.01). In conclusion, the decreased ratio of collagen types I to III seems not only to be the result of a relative increase in the levels of type III procollagen mRNA but also may be the result of an increase of MMP-1 and MMP-13. The data of the present study strongly suggest recurrent inguinal hernias to be a disease of the collagen matrix and result in a clearer understanding of the underlying pathophysiology and may support specific therapeutic strategies in hernia surgery (e.g., surgical meshes).
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PMID:Recurrent inguinal hernia: disease of the collagen matrix? 1191 Apr 70

On the one hand, recurrence rates and postoperative complications following hernia repair are supposed to be influenced by the kind of mesh material used. On the other hand, an impaired collagen metabolism and cleavage within connective tissue has been suggested as decisive factor in the pathogenesis of recurrent hernia formation. The aim of our study was, therefore, to analyze the impact of commonly used mesh materials on quality of collagen deposition, expression of collagenases (matrix metalloproteinases; MMP-1/MMP-13), and specific tissue inhibitors of MMPs (TIMPs) in an animal study. Four different mesh materials were used (Prolene = polypropylene, Mersilene = polyester, and Vypro and Vypro II = combinations of polypropylene and polyglactin) and implanted as abdominal wall replacement in 60 male Wistar rats. Mesh samples were explanted after 3, 21, and 90 days and investigated using immunohistochemistry (expression of MMP-1/MMP-13 and TIMP-1) and cross-polarization microscopy (percentage of collagen type III to overall collagen). Besides an insufficient collagen composition with an increased percentage of collagen type III, we found a complex expression of collagenases and their inhibitors combined with a persistent chronic foreign-body reaction even 90 days after implantation. Except for TIMP-1 expression, which was significantly related to a lowered amount of inflammatory (r = -0.980, p = 0.02) and connective tissue formation (r = -0.951, p = 0.049), there was no relation to the expression of collagenases (MMP-1/MMP-13) with regard to the amount of inflammatory and connective tissue formation despite partly significant differences between implanted polymers.
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PMID:Persistent extracellular matrix remodelling at the interface to polymers used for hernia repair. 1459 34

Incisional hernias represent one of the most common complications of laparotomies. Previous investigations have suggested that a disorder in collagen fiber structure and production level may be an important pathologic cause of abdominal wall hernias. We hypothesized that a cross-examination of multiple extracellular matrix biomarkers might identify underlying defects contributing to the development of hernias. We examined two patient populations: patients with incisional hernias (presenting for hernia repair) and patients with no hernia after previous laparotomy (undergoing a second laparotomy). Patients with previous wound infections, open abdomens, or on steroids were excluded. Fascia samples were obtained from all patients at the time of their second operation and they were studied. Western blots and reverse transcriptase-polymerase chain reaction were used to determine the ratio of type I, III, and IV collagens, as well as matrix metalloproteinase 1 (MMP1) and MMP2 in both groups. Values of P < 0.05 were considered statistically significant. At the protein level, collagen I/III ratio was slightly decreased in patients with incisional hernias compared with those with no hernia, whereas it was significantly decreased at the mRNA transcript level (0.49 vs 1.03, P < 0.01, respectively). The MMP-1 mRNA transcripts were not different in incisional hernia (IH) versus nonincisional hernia, but the MMP-2 level was significantly increased in patients with IH. Reduced collagen I/III and MMP-1/MMP-2 ratios in IH might be consequence of the biological activities between key elements participating in the development of IH after laparotomies. The potential role of MMP-2-specific inhibitors in preventing IH is of significance for future studies.
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PMID:Role of biomarkers in incisional hernias. 1765 92

Surgical treatment of abdominal wall hernia has been based for many decades on observational evidence, as the disease physiopathology was ambiguous. The long-standing hypothesis of abnormal collagen metabolism as a causative factor of hernia disease seems to become substantiated by modern investigations, demonstrating a link between abnormal matrix metalloproteinase (MMP) expression and abdominal wall hernia. Current evidence suggests a strong correlation between MMP-2 and direct inguinal hernia, while the role of this MMP in indirect, incisional and recurrent hernias has not been completely elucidated yet. Furthermore, MMP-1 and MMP-13 seem to be implicated in the physiopathology of recurrent hernia, while limited data link MMP-1 also with incisional hernia formation. Despite the importance of MMP-9 in wound healing mechanisms, its role in hernia pathogenesis has not been adequately investigated. Future research is expected to decipher the complex physiopathological mechanisms of hernia development and provide a basis for potential therapeutic applications.
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PMID:The role of matrix metalloproteinases in the pathogenesis of abdominal wall hernias. 1965 68

Incisional hernia formation is a common complication to laparotomy and possibly associated with alterations in connective tissue metabolism. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are closely involved in the metabolism of the extracellular matrix. Our aim was to study serum levels of multiple MMPs and TIMPs in patients with and without incisional hernia. Out of 305 patients who underwent laparotomy, 79 (25.9%) developed incisional hernia over a median follow-up period of 3.7 years. Pooled sera from a subset (n = 72) of these patients were screened for MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-10, MMP-12, MMP-13, TIMP-1, TIMP-2, and TIMP-4 using a multiplex sandwich fluorescent immunoassay supplemented with gelatin zymography. The screening indicated differences in serum MMP-9 and TIMP-1 levels. Consequently, MMP-9 and TIMP-1 levels were measured in serum in the whole patient cohort with enzyme-linked immunosorbent assay. There were no significant differences in either MMP-9 (p = 0.411) or TIMP-1 (p = 0.679) levels between hernia and hernia-free patients. MMP-9 was significantly increased in smokers compared with nonsmokers (p = 0.016). In conclusion, a possible involvement of MMPs and TIMPs in the pathogenesis of incisional hernia formation was not reflected systemically.
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PMID:Circulating levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with incisional hernia. 2392 24