elastin and Hernia--Inguinal

Abdominal aortic aneurysms (AAAs) and abdominal wall hernias represent chronic degenerative conditions. Both aortic aneurysms and inguinal hernias share common epidemiologic features, and several investigators have found an increased propensity for hernia development in patients treated for aortic aneurysms. Chronic inflammation and dysregulation in connective tissue metabolism constitute underlying biological processes, whereas genetic influences appear to be independently associated with both disease states. A literature review was conducted to identify all published evidence correlating aneurysms and hernias to a common pathology.. PubMed/Medline was searched for studies investigating the clinical, biochemical, and genetic associations of AAAs and abdominal wall hernias. The literature was searched using the MeSH terms "aortic aneurysm, abdominal," "hernia, inguinal," "hernia, ventral," "collagen," "connective tissue," "matrix metalloproteinases," and "genetics" in all possible combinations. An evaluation, analysis, and critical overview of current clinical data and pathogenic mechanisms suggesting an association between aneurysms and hernias were undertaken.. Ample evidence lending support to the clinical correlation between AAAs and abdominal wall hernias exists. Pooled analysis demonstrated that patients undergoing aortic aneurysm repair through a midline abdominal incision have a 2.9-fold increased risk of developing a postoperative incisional hernia compared with patients treated for aortoiliac occlusive disease (odds ratio, 2.86; 95% confidence interval, 1.97-4.16; P < .00001), whereas the risk of inguinal hernia was 2.3 (odds ratio, 2.30; 95% confidence interval, 1.52-3.48; P < .0001). Emerging evidence has identified inguinal hernia as an independent risk factor for aneurysm development. Although mechanisms of extracellular matrix remodeling and the imbalance between connective tissue degrading enzymes and their inhibitors instigating inflammatory responses have separately been described for both disease states, comparative studies investigating these biological processes in aneurysm and hernia populations are scarce. A genetic predisposition has been documented in familial and observational segregation studies; however, the pertinent literature lacks sufficient supporting evidence for a common genetic basis for aneurysm and hernia.. Insufficient data are currently available to support a systemic connective tissue defect affecting the structural integrity of the aortic and abdominal wall. Future investigations may elucidate obscure aspects of aneurysm and hernia pathophysiology and create novel targets for pharmaceutical and gene strategies for disease prevention and treatment.

Topics: Aortic Aneurysm, Abdominal; Collagen; Connective Tissue Diseases; Elastin; Genetic Predisposition to Disease; Hernia, Abdominal; Hernia, Inguinal; Humans; Matrix Metalloproteinases; Odds Ratio; Risk Assessment; Risk Factors; Vascular Surgical Procedures

Elastin-driven genetic diseases are a group of complex diseases driven by elastin protein insufficiency and dominant-negative production of aberrant protein, including supravalvular aortic stenosis (SVAS) and autosomal dominant cutis laxa. Here, a Chinese boy with a novel nonsense mutation in the ELN gene is reported.. We report a 1-year-old boy who presented with exercise intolerance, weight growth restriction with age, a 1-year history of heart murmur, and inguinal hernia. Gene sequencing revealed a novel nonsense mutation in the ELN gene (c.757 C > T (p.Gln253Ter), NM_000501.4). Due to severe branch pulmonary artery stenosis, the reconstruction of the branch pulmonary artery with autologous pericardium was performed. The inguinal hernia repair was performed 3 months postoperatively. After six months of outpatient follow-up, the child recovered well, gained weight with age, and had no special clinical symptoms.. We identified a de novo nonsense mutation in the ELN gene leading to mild SVAS and severe branch pulmonary artery stenosis. A new phenotype of inguinal hernia was also needed to be considered for possible association with the ELN gene. Still, further confirmation will be necessary.

Topics: Aortic Stenosis, Supravalvular; Child; Codon, Nonsense; Elastin; Hernia, Inguinal; Humans; Infant; Male; Mutation; Stenosis, Pulmonary Artery

This basic research aimed to detect the inner-correlation of EGF containing fibulin extracellular matrix protein 1 (EFEMP1), TIMP metallopeptidase inhibitor 3 (TIMP3), matrix metalloprotease 9 (MMP9), elastin (ELN) in direct inguinal hernia (IH), and their effect on fibroblasts motility.. Transversalis fascia samples from 20 direct IH patients and 20 varicocele (served as controls) patients were collected for detecting EFEMP1, TIMP3, MMP9 and ELN expressions by immunohistochemistry assay. Fibroblasts L929 cells were transfected with EFEMP1 overexpression plasmid or knock-down plasmid to investigate the influence of EFEMP1 dysregulation on L929 cell migration, invasion, TIMP3, MMP9 and ELN expressions. Additionally, rescue experiments were performed by adding TIMP3 knockdown plasmid to the EFEMP1-overexpressed L929 cells.. Transversalis fascia EFEMP1, TIMP3 and ELN expressions were decreased, but MMP9 expression was increased in IH patients compared with controls. In IH patients, EFEMP1 was not correlated with TIMP3, but positively correlated with ELN and negatively correlated with MMP9; TIMP3 negatively correlated with MMP9, but positively correlated with ELN. Overexpression of EFEMP1 did not affect TIMP3 expression but increased ELN expression and decreased MMP9 expression in L929 cells. In addition, EFEMP1 suppressed L929 cell migration and invasion. The following rescue experiments indicated that silencing TIMP3 attenuated the effect of EFEMP1 overexpression on MMP9 and ELN expressions as well as the effect of EFEMP1 overexpression on cell migration and invasion in L929 cells.. EFEMP1 is downregulated in direct IH, and it regulates ELN homoeostasis as well as fibroblast mobility via interacting with TIMP3.

Topics: Animals; Cell Line; Cell Movement; Elastin; Extracellular Matrix Proteins; Fibroblasts; Hernia, Inguinal; Homeostasis; Humans; Male; Mice; Tissue Inhibitor of Metalloproteinase-3

The underlying pathology of inguinal hernia is still not fully known; thus, further investigations of genetic backgrounds is needed. Here, we aimed to identify genetic factors attributing to inguinal hernias and explore the polygenic architecture of which some components are population-specific, while others are more common among populations.. We performed a genome-wide association study (GWAS) on subjects with inguinal hernias using BioBank Japan (BBJ) data with 1,983 cases and 172,507 controls, followed by a trans-ethnic meta-analysis with UK Biobank (UKBB) data. We performed downstream analyses in order to identify the mechanisms underlying inguinal hernias supported by genetic findings.. We identified a locus closest to ELN, which encodes elastin, at the GWAS significant level. The trans-ethnic meta-analysis revealed 23 additional significant loci, including five loci newly identified not significant in BBJ or UKBB GWAS: TGFB2, RNA5SP214/VGLL2, LOC646588, HMCN2, and ATP5F1CP1/CDKN3. Downstream analyses revealed the overlap of GWAS significant signals in extracellular components, including elastin fiber formation. We also found a highly shared polygenic architecture across different populations (trans-ethnic genetic-effect correlation = 0•77, standard error = 0•26) and population-specific lead variants in ELN, indicating the critical role of elastin in inguinal hernias.. We identified a significant locus of the ELN gene in the Japanese population and five additional loci across different populations. Downstream analyses revealed highly shared genetic architectures across populations and highlighted the important roles of extracellular components in the development of inguinal hernias. These findings deepen our understanding of the mechanisms underlying inguinal hernia.. The Japan Agency for Medical Research and Development (AMED) (Grant Number: JP19km0605001).

Topics: Elastin; Female; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Hernia, Inguinal; Humans; Male; Middle Aged; Multifactorial Inheritance

Altered composition of collagen and elastin in abdominal fascia has been linked with the pathogenesis of hernias. This has not been studied amongst Africans who have hernia presentations which vary significantly from Caucasian cohorts. The aim of this study was to determine, and compare, the collagen and elastin contents of the transversalis fascia and rectus sheath of inguinal hernia patients with non-hernia controls.. Twenty-five patients with solitary, primary, uncomplicated inguinal hernia and twenty-five non-hernia controls were evaluated. Biopsies of the transversalis fascia and anterior rectus sheath were stained with Masson Trichrome and Verhöeff van-Gieson to isolate collagen and elastin respectively, which were quantified using the ImageJ/Fiji® image analysis software.. Inguinal hernia patients were aged 19-85 years with a mean age of 45.2 years, mean body mass index (BMI) of 23.3 kg/m

Topics: Abdominal Wall; Adult; Africa; Aged; Aged, 80 and over; Elastin; Fascia; Female; Hernia, Inguinal; Humans; Male; Middle Aged; Young Adult

Williams-Beuren syndrome is a rare neurodevelopmental disorder, characterized by congenital heart defects, abnormal facial features, mental retardation with specific cognitive and behavioral profile, growth hormone deficiency, renal and skeletal anomalies, inguinal hernia, infantile hypercalcaemia. We report a case with Williams-Beuren syndrome associated with a single kidney and nephrocalcinosis complicated by hypercalcaemia. A male infant, aged 20 months presented growth retardation associated with a psychomotor impairment, dysmorphic features and nephrocalcinosis. He had also hypercalciuria and hypercalcemia. Echocardiography was normal. DMSA renal scintigraphy showed a single functioning kidney. The FISH generated one ELN signal in 20 metaphases read and found the presence of ELN deletion, with compatible Williams-Beuren syndrome.

Topics: Elastin; Hernia, Inguinal; Humans; Hypercalcemia; Infant; Kidney; Male; Nephrocalcinosis; Williams Syndrome

Elastin gene mutations have been associated with a variety of phenotypes. Autosomal dominant cutis laxa (ADCL) is a rare disorder that presents with lax skin, typical facial characteristics, inguinal hernias, aortic root dilatation and pulmonary emphysema. In most patients, frameshift mutations are found in the 3' region of the elastin gene (exons 30-34) which result in a C-terminally extended protein, though exceptions have been reported.. We clinically and molecularly characterized the thus far largest cohort of ADCL patients, consisting of 19 patients from six families and one sporadic patient.. Molecular analysis showed C-terminal frameshift mutations in exon 30, 32, and 34 of the elastin gene and identified a mutational hotspot in exon 32 (c.2262delA). This cohort confirms the previously reported clinical constellation of skin laxity (100%), inguinal hernias (51%), aortic root dilatation (55%) and emphysema (37%).. ADCL is a clinically and molecularly homogeneous disorder, but intra- and interfamilial variability in the severity of organ involvement needs to be taken into account. Regular cardiovascular and pulmonary evaluations are imperative in the clinical follow-up of these patients.

Topics: Cutis Laxa; Elastin; Exons; Female; Frameshift Mutation; Genes, Dominant; Hernia, Inguinal; Humans; Male; Pulmonary Emphysema; Severity of Illness Index; Skin

The aetiology of inguinal hernia involves changes in collagen turnover and metalloproteinase expression; yet it is not known whether the elastic fibre system could also be affected. This study was designed to compare the expression of tropoelastin (TE), lysyl oxidase-like 1 (LOXL-1) and elastase in the transversalis fascia of patients with and without inguinal hernia.. Transversalis fascia (TF) specimens were obtained from patients undergoing surgery for direct or indirect inguinal hernia (n = 20 each) and from multi-organ donors during organ procurement (controls, n = 16). The specimens were divided according to age (20-40/41-60 years). Tissues were immunohistochemically labelled using anti-tropoelastin, anti-LOXL-1 and anti-elastase antibodies and subjected to Western blot analysis. Relative amounts of LOXL-1 and TE mRNA were determined by real time RT-PCR in cultured cells obtained from the TF of patients and controls.. Significantly lower TE and LOXL-1 levels were observed in patients with direct inguinal hernia compared with controls or those with indirect hernia. In contrast, patients with direct inguinal hernia showed significantly higher elastase expression. In fibroblasts isolated from the TF, relative amounts of tropoelastin mRNA were lower for the hernia groups but differences were not significant. LOXL-1 mRNA levels were significantly lower in the direct hernia group compared to controls.. Our findings suggest that impaired elastic fibre function in the transversalis fascia of patients with direct inguinal hernia, reflected by diminished elastin synthesis and its enhanced enzyme degradation, contributes to the development of this type of hernia.

Topics: Adult; Blotting, Western; Case-Control Studies; Cell Culture Techniques; Elastin; Hernia, Inguinal; Humans; Immunohistochemistry; Middle Aged; Protein-Lysine 6-Oxidase; Reverse Transcriptase Polymerase Chain Reaction

It has been claimed that inguinal hernia is not a local disease; it is a local manifestation of a systemic disorder of collagen metabolism. Previous studies have shown that patients with inguinal hernia have some anomalies in collagen metabolism and changed ratio of collagen types.. To search the changes in collagen and elastic fiber contents of the skin, rectus sheath, transversalis fascia and peritoneum in primary inguinal hernia patients.. Twenty patients operated on for inguinal hernia (HR) included in the study (11 direct and 9 indirect). Nine patients underwent open cholecystectomy served as the control group (CC). A 0.5 x 1 cm. tissue was sampled from skin, rectus sheath, transversalis fascia and peritoneum in HR group. Skin, rectus sheath and peritoneum samples were taken from the patients in CC group. The sections of those samples were submitted to two different staining methods: "Masson's trichrome" for collagen and "van Gieson" for elastin fibers and graded with light microscopy.. The rectus sheath samples of CC had higher staining scores for both collagen and elastin fibers in comparison with HR (p = 0.032 and p = 0.026, respectively). CC had a significantly higher score for collagen in peritoneum samples (p = 0.019). There were no statistically significant differences between the patients with direct and indirect inguinal hernias for collagen or elastin fibers scores in skin, rectus sheath, transversalis fascia and peritoneum samples.. These findings, which concur with most of the previous studies, support the theory that inguinal hernia may not be merely a local disease and can be more generalized, at least a regional connective tissue disorder. Regarding the difference between direct and indirect hernias, it could not be possible to report a certain answer, and this issue should be considered together with previous quantitative researches and more sophisticated studies may take place in the future (Tab. 2, Fig. 2, Ref. 23).

Topics: Collagen; Elastin; Fascia; Hernia, Inguinal; Humans; Middle Aged; Peritoneum; Rectus Abdominis; Skin