scholarly journals Effect of Captopril and Melatonin on Fibrotic Rebuilding of the Aorta in 24 Hour Light-Induced Hypertension

2013 ◽  
pp. S135-S141 ◽  
Author(s):  
K. REPOVÁ-BEDNÁROVÁ ◽  
S. AZIRIOVÁ ◽  
J. HRENÁK ◽  
K. KRAJČÍROVIČOVÁ ◽  
M. ADAMCOVÁ ◽  
...  

Chronic continuous light exposure leads to melatonin deficiency along with complex neurohumoral activation resulting in hypertension development in rats. The aim of this study was to show, whether continuous light induces fibrotic rebuilding of the aorta and whether the treatment with melatonin or angiotensin converting enzyme inhibitor captopril can prevent these potential alterations. In a six-week experiment, 3-month-old Wistar rats were divided into 4 groups (ten per group): controls, rats exposed to continuous light, exposed to continuous light plus treated with captopril (100 mg/kg/24 h) and exposed to continuous light plus treated with melatonin (10 mg/kg/24 h). Systolic blood pressure (SBP) and collagen type I and III in the media of thoracic aorta were measured. Continuous light induced hypertension and fibrotic rebuilding of the aorta in terms of enhancement of collagen I and III concentration in the aortic media. Both captopril and melatonin prevented SBP rise and reduced collagen III concentration in the aorta. However, only melatonin reduced collagen I and the sum of collagen I and III in the aortic tissue. We conclude that in continuous light-induced hypertension, administration of melatonin, along with SBP reduction, decreases collagen I and III concentration in the aorta. It is suggested that antifibrotic effect of melatonin may reduce the stiffness of the aorta and small arteries and beneficially influence the nature of the pulse wave and peripheral vascular resistance.

2007 ◽  
pp. S71-S76
Author(s):  
Ľ Paulis ◽  
R Važan ◽  
F Šimko ◽  
O Pecháňová ◽  
J Styk ◽  
...  

Although exposure to continuous light is associated with hypertension and modulates the outcome of ischemia-reperfusion injury, less attention has been paid to its effects on cardiac morphology. We investigated whether 4-week exposure of experimental rats to continuous 24 h/day light can modify cardiac morphology, with focus on heart weight, fibrosis and collagen I/III ratio in correlation with NO-synthase expression. Two groups of male adult Wistar rats were studied: controls exposed to normal light/dark cycle (12 h/day light, 12 h/day dark) and rats exposed to continuous light. After 4 weeks of treatment the absolute and the relative heart weights were determined and myocardial fibrosis and collagen type I/III ratio were evaluated using picrosirius red staining. Endothelial and inducible NO-synthase expression was detected immunohistochemically. The exposure of rats to continuous light resulted in an increase of body weight with proportionally increased heart weight. Myocardial fibrosis remained unaffected but collagen I/III ratio increased. Neither endothelial nor inducible NO-synthase expression was altered in light-exposed rats. We conclude that the loss of structural homogeneity of the myocardium in favor of collagen type I might increase myocardial stiffness and contribute to functional alterations after continuous light exposure.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrew Hall ◽  
Corina Cotoi ◽  
Tu Vinh Luong ◽  
Jennifer Watkins ◽  
Prithi Bhathal ◽  
...  

AbstractThe histological distinction between acute and chronic liver injury is a challenging aspect of liver histopathology. It is traditionally based on the interpretation of morphological changes to the extracellular matrix (ECM) at sites of hepatocyte loss using histochemical stains. Our aim was to investigate whether immunohistochemistry and multiplexing for collagen type (I & III) and elastic fibres and a modified Victoria blue method could be helpful. We studied 43 livers removed at transplantation for acute liver failure (ALF, 20 cases) or cirrhosis (23) plus 8 normal controls. In ALF the periportal ECM was normal in 2 cases, contained mainly collagen I associated with a ductular reaction in 6 cases, and delicate elastic strands in 11 cases. Periportal deposition of mainly collagen I and mature elastic fibres was observed in cirrhosis. In ALF the perisinusoidal ECM was intact in 4 cases, collapsed or condensed but of normal composition (predominantly collagen III) in 2 cases, and collapsed and condensed containing mostly collagen I in 17 cases (7 including delicate immature elastic strands). In contrast, bridging fibrous septa of cirrhosis contained abundant collagen 1 and bundles of mature elastin. We propose the use of a scale and the use of immunohistochemistry and multiplexing in additional to histochemical stains to characterise the ECM changes in acute and chronic liver injury.


2021 ◽  
Author(s):  
Andrew Hall ◽  
Corina Cotoi ◽  
Tu Vinh Luong ◽  
Jennifer Watkins ◽  
Prithi Bhathal ◽  
...  

Abstract The histological distinction between acute and chronic liver injury is a challenging aspect of liver histopathology. It is traditionally based on the interpretation of morphological changes to the extracellular matrix (ECM) at sites of hepatocyte loss using histochemical stains. Our aim was to investigate whether immunohistochemistry and multiplexing for collagen type (I & III) and elastic fibres and a modified Victoria blue method could be helpful. We studied 43 livers removed at transplantation for acute liver failure (ALF, 20 cases) or cirrhosis (23) plus 8 normal controls. In ALF the periportal ECM was normal in 2 cases, contained collagen I associated with a ductular reaction in 6 cases, and delicate elastic strands in 11 cases. Periportal deposition of collagen I and mature elastic fibres was observed in cirrhosis. In ALF the perisinusoidal ECM was intact in 4 cases, collapsed or condensed but of normal composition (collagen III) in 2 cases, and collapsed and condensed containing collagen I in 17 cases (7 including delicate immature elastic strands). In contrast, bridging fibrous septa of cirrhosis contained abundant collagen 1 and bundles of mature elastin. We propose the use of a scale and the use of immunohistochemistry and multiplexing in additional to histochemical stains to characterise the ECM changes in acute and chronic liver injury.


Reproduction ◽  
2001 ◽  
pp. 581-586 ◽  
Author(s):  
I Walter ◽  
J Handler ◽  
M Reifinger ◽  
C Aurich

Periglandular fibrosis and cystic dilation of uterine glands are associated with equine endometriosis. The presence of extracellular matrix proteins (collagen type I, III and IV, laminin and fibronectin) in healthy and endometriotic specimens was demonstrated by immunohistochemistry. The distribution of collagen I, but not collagen III, was dependent on the stage of the oestrous cycle. The arrangement of collagen I and collagen III in endometriotic specimens was similar to that in normal endometrium. In periglandular fibrosis, collagen IV, laminin and fibronectin deposition outside the basement membrane was observed. In these regions, stromal cells were characterized immunohistochemically as myofibroblasts because of their expression of a-smooth muscle actin, and occasionally tropomyosin and desmin. Periglandular differentiation of contractile cells could be interpreted as a reaction to support the extrusion of secretions in cystic dilated glands. Moreover, the changes of extracellular matrix proteins are characteristic for neoplastic lesions, although further development of endometriosis to benign or malignant tumours is not known in horses. Knowledge of the factors responsible for these fibroblastic modulations may be the key to explaining the pathogenesis of endometriosis.


2009 ◽  
Vol 24 (6) ◽  
pp. 476-483 ◽  
Author(s):  
Danielle Duck Schulz ◽  
Nicolau Gregori Czeczko ◽  
Osvado Malafaia ◽  
Gustavo Justo Schulz ◽  
Leticia Elizabeth A. Czeczko ◽  
...  

PURPOSE: To compare polyester with absorbable layer prosthesis with collagen-elastin/polypropylene prosthesis in the repair of abdominal wall defects. METHODS: The 16 studied rabbits were divided in groups A and B (euthanized on the 30th and 60th days, after the implant of the mesh). The animals underwent laparotomy and received a 2cm wall "defect" on each side of the Alba linea. The repair was made with the suture of a polyester mesh with absorbable film on the left side of the Alba Linea and with collagen-elastin/polypropylene mesh on the right side. Adherences were classified according to Nair Score and microscopic evaluation observing types I and III collagen formation and other immunohistochemical analyses. RESULTS: There were no significant differences in adhesion formation. The collagen type I showed higher deposition in polyester with absorbable layer. In group B, the difference between the meshes was significant, with higher collagen III deposition in polyester with absorbable layer (60º P.O.). About the metalloproteinases, the presence of MMP -1 and MMP-8 were about the same; the expression of MMP-13 increased near to the 60th day. CONCLUSIONS: There is no significant difference between the two meshes in adhesion formation and immunohystochemical evaluation. The polyester mesh resorbable film presented a higher deposition of collagen.


2005 ◽  
Vol 26 (9) ◽  
pp. 732-738 ◽  
Author(s):  
Eiichi Uchiyama ◽  
Harold B. Kitaoka ◽  
Zong-Ping Luo ◽  
Joseph P. Grande ◽  
Hideji Kura ◽  
...  

Background: One factor believed to contribute to the development of hallux valgus is an abnormality in collagen structure and makeup of the medial collateral ligament (MCL) of the first metatarsophalangeal joint (MTPJ). We hypothesized that the mechanical properties of the MCL in feet with hallux valgus are significantly different from those in normal feet and that these differences may be related to alterations in the type or distribution of collagen fibers at the interface between the MCL and the bone. Materials and Methods: Seven normal fresh-frozen cadaver feet were compared to four cadaver feet that had hallux valgus deformities. The MCL mechanical properties, structure of collagen fibers, and content proportion of type I and type III collagen were determined. Results: The load-deformation and stress-strain curves were curvilinear with three regions: laxity, toe, and linear regions. Laxity of the MCL in feet with hallux valgus was significantly larger than that of normal feet ( p = 0.022). Stiffness and tensile modulus in the toe region in feet with hallux valgus were significantly smaller than those in normal feet ( p = 0.004); however, stiffness and tensile modulus in the linear region were not significantly different. The MCL collagen fibrils in the feet with hallux valgus had a more wavy distribution than the fibrils in the normal feet. Conclusions: In general, strong staining for collagen III and to a lesser extent, collagen I was observed at the interface between the MCL and bone in the feet with hallux valgus but not in the normal feet. These results indicate that the abnormal mechanical properties of the MCL in feet with hallux valgus may be related to differences in the organization of collagen I and collagen III fibrils.


2020 ◽  
Vol 133 (23) ◽  
pp. jcs248278 ◽  
Author(s):  
Ana M. Diaz-Espinosa ◽  
Patrick A. Link ◽  
Delphine Sicard ◽  
Ignasi Jorba ◽  
Daniel J. Tschumperlin ◽  
...  

ABSTRACTMatrix resorption is essential to the clearance of the extracellular matrix (ECM) after normal wound healing. A disruption in these processes constitutes a main component of fibrotic diseases, characterized by excess deposition and diminished clearance of fibrillar ECM proteins, such as collagen type I. The mechanisms and stimuli regulating ECM resorption in the lung remain poorly understood. Recently, agonism of dopamine receptor D1 (DRD1), which is predominantly expressed on fibroblasts in the lung, has been shown to accelerate tissue repair and clearance of ECM following bleomycin injury in mice. Therefore, we investigated whether DRD1 receptor signaling promotes the degradation of collagen type I by lung fibroblasts. For cultured fibroblasts, we found that DRD1 agonism enhances extracellular cleavage, internalization and lysosomal degradation of collagen I mediated by cathepsin K, which results in reduced stiffness of cell-derived matrices, as measured by atomic force microscopy. In vivo agonism of DRD1 similarly enhanced fibrillar collagen degradation by fibroblasts, as assessed by tissue labeling with a collagen-hybridizing peptide. Together, these results implicate DRD1 agonism in fibroblast-mediated collagen clearance, suggesting an important role for this mechanism in fibrosis resolution.This article has an associated First Person interview with the first author of the paper.


2011 ◽  
Vol 300 (4) ◽  
pp. C907-C918 ◽  
Author(s):  
Matilde Alique ◽  
Laura Calleros ◽  
Alicia Luengo ◽  
Mercedes Griera ◽  
Miguel Ángel Iñiguez ◽  
...  

Glomerular diseases are characterized by a sustained synthesis and accumulation of abnormal extracellular matrix proteins, such as collagen type I. The extracellular matrix transmits information to cells through interactions with membrane components, which directly activate many intracellular signaling events. Moreover, accumulating evidence suggests that eicosanoids derived from cyclooxygenase (COX)-2 participate in a number of pathological processes in immune-mediated renal diseases, and it is known that protein kinase B (AKT) may act through different transcription factors in the regulation of the COX-2 promoter. The present results show that progressive accumulation of collagen I in the extracellular medium induces a significant increase of COX-2 expression in human mesangial cells, resulting in an enhancement in PGE2 production. COX-2 overexpression is due to increased COX-2 mRNA levels. The study of the mechanism implicated in COX-2 upregulation by collagen I showed focal adhesion kinase (FAK) activation. Furthermore, we observed that the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway by collagen I and collagen I-induced COX-2 overexpression was abolished by PI3K and AKT inhibitors. Additionally, we showed that the cAMP response element (CRE) transcription factor is implicated. Finally, we studied COX-2 expression in an animal model, NG-nitro-l-arginine methyl ester hypertensive rats. In renal tissue and vascular walls, COX-2 and collagen type I content were upregulated. In summary, our results provide evidence that collagen type I increases COX-2 expression via the FAK/PI3K/AKT/cAMP response element binding protein signaling pathway.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Fedor Simko ◽  
Olga Pechanova ◽  
Kristina Repova Bednarova ◽  
Kristina Krajcirovicova ◽  
Peter Celec ◽  
...  

Exposure of rats to continuous light attenuates melatonin production and results in hypertension development. This study investigated whether hypertension induced by continuous light (24 hours/day) exposure induces heart and aorta remodelling and if these alterations are prevented by melatonin or angiotensin converting enzyme inhibitor captopril. Four groups of 3-month-old male Wistar rats (10 per group) were treated as follows for six weeks: untreated controls, exposed to continuous light, light-exposed, and treated with either captopril (100 mg/kg/day) or melatonin (10 mg/kg/day). Exposure to continuous light led to hypertension, left ventricular (LV) hypertrophy and fibrosis, and enhancement of the oxidative load in the LV and aorta. Increase in systolic blood pressure by continuous light exposure was prevented completely by captopril and partially by melatonin. Both captopril and melatonin reduced the wall thickness and cross-sectional area of the aorta and reduced the level of oxidative stress. However, only captopril reduced LV hypertrophy development and only melatonin reduced LV hydroxyproline concentration in insoluble and total collagen in rats exposed to continuous light. In conclusion, captopril prevented LV hypertrophy development in the continuous light-induced hypertension model, while only melatonin significantly reduced fibrosis. This antifibrotic action of melatonin may be protective in hypertensive heart disease.


2020 ◽  
Vol 9 (4) ◽  
pp. 24-30
Author(s):  
A.V. Asaturova ◽  
◽  
N.M. Faizullina ◽  
M.V. Bobkova ◽  
A.S. Arakelyan ◽  
...  

Introduction. Female patients with Mayer–Rokitansky–Küster–Hauser syndrome (MRKH) have high stigma scores; the condition severely affects the reproductive system. The study aimed at specification of morphological features and assessment of the maturity of connective tissues of the uterine rudiments in MRKH. Patients and methods. The study included 42 patients with vaginal and uterine aplasia having functioning uterine rudiments and 47 patients of the control group without genital malformations. Age of the patients was 20-24 years in 67.2% of the cases, and 31.2% of the patients were aged ≤ 19, inclusive. Immunohistochemi-cal assay was applied to determine expression levels of collagen I, collagen III, ММР2, ММР9, TIMP1, fibronectin and laminin proteins within the functioning uterine rudiments in comparison with levels of the same proteins in normally developed uterine tissues. Results. Decreased expression of collagen type I and elevated levels of MMP2 and MMP9 proteins in uterine tissues were observed for the group of patients with MRKH. Conclusions. 1) Uterine rudiments in patients with MRKH show variable degree of morphological similarity with the normally developed uterus; 2) The functioning uterine rudiments are subject to the same pathological processes as the normally developed uterus (myoma, endometriosis). 3) The functioning uterine rudiments in patients with MRKH show altered patterns of connective tissue remodeling, with decreased expression of collagen type I and increased expression of matrix metalloproteinases MMP2 and MMP9. Keywords: Müllerian aplasia, uterine rudiments, metalloproteinases, connective tissue remodeling, ММР2, ММР9


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