The present PhD proposes a rigorous evaluation and quantification of pediatric liver allograft fibrosis in 595 liver biopsies of 139 patients from 6 months to 10 years following liver transplantation, analyzing the influence of clinical variables and the immunosuppression on fibrosis progression, as well as the relevance of activated Hepatic Stellate cells (HSCs) in predicting allograft fibrosis development. A novel fibrosis scoring system, the Liver Allograft Fibrosis Score, was designed and validated specifically for allograft fibrosis assessment, categorizing separately sinusoidal, centrilobular and portal fibrosis. Progressive fibrosis was found in 74% of the liver biopsies reviewed. Clinical factors were identified to promote fibrosis in a specific area of the liver parenchyma. The steroid therapy did not contribute to reduce fibrosis. Finally, the high proportion of activated-HSCs found in this population was useful as a predictor of long-term allograft fibrosis development.. [fre] Cette ...
Liver organ fibrosis is the final stage of liver diseases that lead to liver failure and malignancy. gene manifestation was inhibited in the advanced stage of liver fibrosis while transient but prominent MMP13 gene manifestation occurs during the early stage of recovery from experimental rat liver organ fibrosis. It is therefore acceptable to consider that upregulation of MMP13 gene appearance can lead to a consequent upsurge in collagenase activity in fibrotic livers and provide a procedure for antifibrotic therapy in preventing liver organ fibrosis. Since comprehensive regression from advanced cirrhosis is normally both doubtful and controversial it really is even more feasible to build up a secure and efficient method of preventing the development of fibrosis in liver organ disease. In regards to towards the transfer from the MMP gene in to the liver organ youll be able to selectively inject nude DNA in to the liver organ via either the portal vein or the hepatic artery. Gene delivery ...
Background: Cardiac fibrosis contributes to heart failure progression following myocardial infarction (MI) and chronic kidney disease (uremic cardiomyopathy). We examined the effect of the anti-fibrotic agent, tranilast, on cardiac fibrosis in both heart and kidney failure.. Methods: MI was induced by coronary artery ligation in Sprague Dawley (SD) rats, and animals randomized to receive tranilast (300mg/kg/day, p.o.) or vehicle for 28 days. Renal failure was induced by 5/6 nephrectomy (STNx) and animals randomized to receive tranilast (300mg/kg/day, p.o.) or vehicle for 12 weeks. Myocardial tissues were harvested for histological analysis. To determine direct effects of tranilast, cardiac fibrosis independent of any hemodynamic influence, neonatal cardiac fibroblasts (NCF) were stimulated with TGFβ1 in the presence and absence of tranilast and examined for proline incorporation, profibrotic gene and phospho-Smad2 protein expression.. Results: Tranilast treatment in MI animals attenuated the ...
Background: Prognostic value of myocardial fibrosis in patients with non-ischemic idiopathic cardiomyopathy (NICM) is not well-defined. We sought to assess the association of focal and diffuse myocardial fibrosis to left ventricular reversed remodeling.. Methods: Patients with NICM who underwent cardiac MRI and baseline and subsequent follow-up echocardiographic were included in the study. Post-contrast T1 times were measured using Look-Locker gradient echo, and was adjusted for renal function, body size, gadolinium dose and delayed time after Gadolinium injection. Patients were followed over a median time of 29 months (20,37) to evaluate changes of left ventricular end-systolic volume index (LVESVi) over time. Linear Mixed Model was used to assess the relationship between the LVESVi during follow-up,T1 value, and delayed hyperenhancement (DHE).. Results: A total of 103 patients (mean age 51±15 years, 62% male) were included in the analysis. Mean LVEF 32±10%, LVESVi 62±39 ml/m2, and T1 time ...
Cardiac fibrosis as a result of excessive extracellular matrix deposition leads to stiffening of the heart, which can eventually lead to heart failure. An important event in cardiac fibrosis is the transformation of fibroblasts into myofibroblasts, which secrete large amounts of extracellular matrix proteins. While the function of protein-coding genes in myofibroblast activation and fibrosis has been a topic of investigation for a long time, it has become clear that non-coding RNAs also play key roles in cardiac fibrosis. This review discusses the involvement of microRNAs and lncRNAs in cardiac fibrosis and summarizes the issues related to translating these findings into real life therapies. ...
Fibrosis contributes to the development of many diseases and many target molecules are involved in fibrosis. Currently, the majority of fibrosis treatment strategies are limited to specific diseases or organs. However, accumulating evidence demonstrates great similarities among fibroproliferative diseases, and more and more drugs are proved to be effective anti-fibrotic therapies across different diseases and organs. Here we comprehensively review the current knowledge on the pathological mechanisms of fibrosis, and divide factors mediating fibrosis progression into extracellular and intracellular groups. Furthermore, we systematically summarize both single and multiple component drugs that target fibrosis. Future directions of fibrosis drug discovery are also proposed.
Renal fibrosis is a serious clinical problem forming the utmost cause of need for renal replacement therapy. No adequate preventive or curative therapy is available that can be clinically used to specifically target renal fibrosis. The search for new efficacious treatment strategies is therefore warranted. Although in vitro models using homogeneous cell populations have contributed to the understanding of the pathogenetic mechanisms involved in renal fibrosis, these models poorly mimic the complex in vivo milieu. Therefore, here we evaluated a precision-cut kidney slice (PCKS) model as a new, multicellular ex vivo model to study development of fibrosis and the prevention thereof using anti-fibrotic compounds.. Precision-cut slices (200-300 µm thickness) were prepared from healthy C57BL/6 mouse kidneys using a Krumdieck tissue slicer. To induce changes mimicking the fibrotic process, slices were incubated with TGFβ1 (5 ng/ml) for 48 hours in the presence or absence of the anti-fibrotic cytokine ...
Results Nintedanib dose-dependently reduced platelet-derived growth factor-induced and transforming growth factor-β-induced proliferation and migration as well as myofibroblast differentiation and collagen release of dermal fibroblasts from patients with and healthy individuals. Nintedanib also inhibited the endogenous activation of SSc fibroblasts. Nintedanib prevented bleomycin-induced skin fibrosis in a dose-dependent manner and was also effective in the treatment of established fibrosis. Moreover, treatment with nintedanib ameliorated fibrosis in the chronic graft-versus-host disease model and in tight-skin-1 mice in well-tolerated doses. ...
Both groups survived long-term (,100 days). The allogeneic grafts were infiltrated by significantly increased numbers of CD4+ (P ,0.0001), CD8+ (P ,0.0001), and CD11b+ cells (P = 0.0065) by day 100. Furthermore, elevated IL-13 levels (P = 0.0003) and numbers of infiltrating IL-13+ cells (P = 0.0037), together with an expression of IL-13Rα2, were detected only within allografts. The expression of IL-13 and IL-13Rα2 resulted in significantly increased TGF-β1 levels (P ,0.0001), higher numbers of CD11bhighGr1intermediateTGF-β1+ cells, and elevated cardiac collagen deposition (P = 0.0094). The allograft fibrosis found in these experiments was accompanied by upregulation of multiple profibrotic genes, which was confirmed by immunohistochemical stainings of allograft tissue. Blockage of the IL-13/TGF-β1 interaction by IL-13Rα2 siRNA led to lower numbers of CD11bhighGr1intermediateTGF-β1+, CD4+, CD8+, and CD11b+ cells, and prevented collagen deposition (P = 0.0018) within these allografts ...
Renal fibrosis is a main cause of end-stage renal disease. Clinically, there is no beneficial treatment that can effectively reverse the progressive loss of renal function. We recently synthesized a novel proteolysis-resistant cyclic helix B peptide (CHBP) that exhibits promising renoprotective effects. In this study, we evaluated the effect of CHBP on renal fibrosis in an in vivo ischemia reperfusion injury (IRI) model and in vitro TGF-β-stimulated tubular epithelial cells (TCMK-1 and HK-2) model. In the IRI in vivo model, mice were randomly divided into sham (sham operation), IR and IR + CHBP groups (n = 6). CHBP (8 nmol/kg) was administered intraperitoneally at the onset of reperfusion, and renal fibrosis was evaluated at 12 weeks post-reperfusion. Our results showed that CHBP markedly attenuated the IRI-induced deposition of collagen I and vimentin. In the in vitro model, CHBP reversed the TGF-β-induced down-regulation of E-cadherin and up-regulation of α-SMA and vimentin. Furthermore, CHBP
LONDON, Oct. 19, 2017 /PRNewswire/ -- Summary
Global Markets Directs latest Pharmaceutical and Healthcare disease pipeline guide Kidney Fibrosis - Pipeline Review, H2 2017, provides an overview of the Kidney Fibrosis (Genito Urinary System And Sex Hormones) pipeline landscape.



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Summary Latest Pharmaceutical and Healthcare disease pipeline guide Kidney Fibrosis Pipeline Review, H1 2017, provides an overview of the Kidney Fibrosis (
TY - JOUR. T1 - Intractable diarrhea caused by intestinal fibrosis. AU - Ferretti, F.. AU - Bella, S.. AU - Boldrini, R.. AU - Gambarara, M.. AU - Capuano, L.. AU - Papadatou, B.. AU - Bosman, C.. AU - Diamanti, A.. AU - Castro, M.. PY - 1998. Y1 - 1998. UR - http://www.scopus.com/inward/record.url?scp=0031710426&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0031710426&partnerID=8YFLogxK. U2 - 10.1016/S0041-1345(98)00717-9. DO - 10.1016/S0041-1345(98)00717-9. M3 - Article. C2 - 9745478. AN - SCOPUS:0031710426. VL - 30. SP - 2541. EP - 2542. JO - Transplantation Proceedings. JF - Transplantation Proceedings. SN - 0041-1345. IS - 6. ER - ...
Fibrosis occurs when transforming growth factor-β (TGF-β) signaling is not attenuated after wound healing and fibroblasts remain activated, resulting in tissue scarring. The mechanisms that turn off TGF-β signaling after wound healing and inhibit this pathway in general are not well-understood. Palumbo-Zerr et al. noted that the abundance of the orphan receptor NR4A1 (nuclear receptor 4A1) was increased at the mRNA and protein levels in the fibrotic skin of patients with systemic sclerosis and in the skin of mice overexpressing a constitutively active TGF-β receptor type I (TBRI), which are a model for fibrosis. TGF-β stimulated the increased expression of NR4A1 through a complex containing the transcriptional effectors SMAD3, SMAD4, and SP1. Global Nr4a1 deficiency enhanced the expression of TGF-β target genes and fibrosis in mice overexpressing TBRI, as well as in other mouse models of fibrosis, including pulmonary fibrosis induced by bleomycin. Nr4a1-/- fibroblasts deposited more ...
Myofibroblas adalah sumber utama komponen matriks ekstraseluler yang terakumulasi selama fibrosis jaringan, dan hepatic stellate cells (HSC) dipercaya menjadi sumber utama myofibroblas di dalam liver. Sampai saat ini, sistem yang kuat untuk memanipulasi sel-sel ini secara genetik belum dikembangkan. Dilaporkan bahwa Cre di bawah kontrol promoter Pdgfrb (Pdgfrb-Cre) menginaktivasi gen loxP-flanked di dalam tikus HSC…
Progression of renal fibrosis: the underestimated role of endothelial alterations. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Causes of Muscular fibrosis, multifocal - obstructed vessels including triggers, hidden medical causes of Muscular fibrosis, multifocal - obstructed vessels, risk factors, and what causes Muscular fibrosis, multifocal - obstructed vessels.
Fibrosis refers to a phenomenon of development of excessive connective tissue as a result of some injury or some disease. It results in formation of a laye
One of the most difficult problems to tackle is the development of fibrosis (scarring) which is a direct consequence of the kidneys limited capacity to regenerate after injury. Such fibrosis can develop into a life-threatening condition. At present we may be able to halt the progression of renal scarring, but thats all. Early detection of CKD would allow improved disease management.. One thing to remember is that the aetiology of CKD is diverse. It includes immunological, mechanical, metabolic and toxic origins amongst others. To complicate the matter further it will affect three functional compartments of the kidney: the vasculature, glomerulus and tubulointerstitium . Therefore, it is extremely challenging to choose the optimal therapy. At present, renal biopsy offers one of the best methods to test for the presence of fibrosis but it requires surgical intervention, is painful, and it is very costly. A non-invasive method to detect the early incidence of such fibrosis would be ...
Main Zone Tuner Frequency Sirius 001,@TFQ:000001. Main Zone Tuner Frequency Sirius 002,@TFQ:000002. Main Zone Tuner Frequency Sirius 003,@TFQ:000003. Main Zone Tuner Frequency Sirius 004,@TFQ:000004. Main Zone Tuner Frequency Sirius 005,@TFQ:000005. Main Zone Tuner Frequency Sirius 006,@TFQ:000006. Main Zone Tuner Frequency Sirius 007,@TFQ:000007. Main Zone Tuner Frequency Sirius 008,@TFQ:000008. Main Zone Tuner Frequency Sirius 009,@TFQ:000009. Main Zone Tuner Frequency Sirius 010,@TFQ:000010. Main Zone Tuner Frequency Sirius 011,@TFQ:000011. Main Zone Tuner Frequency Sirius 012,@TFQ:000012. Main Zone Tuner Frequency Sirius 013,@TFQ:000013. Main Zone Tuner Frequency Sirius 014,@TFQ:000014. Main Zone Tuner Frequency Sirius 015,@TFQ:000015. Main Zone Tuner Frequency Sirius 016,@TFQ:000016. Main Zone Tuner Frequency Sirius 017,@TFQ:000017. Main Zone Tuner Frequency Sirius 018,@TFQ:000018. Main Zone Tuner Frequency Sirius 019,@TFQ:000019. Main Zone Tuner Frequency Sirius 020,@TFQ:000020. Main Zone ...
Fibrosis pulmoner (pulmonary fibrosis) adalah kondisi di mana jaringan parut yang berlebihan terbentuk di paru-paru. Kondisi ini membuat paru-paru menjadi kaku dan mengurangi jumlah luas permukaan yang tersedia untuk pertukaran udara.. ...
By default, all articles on GreenMedInfo.com are sorted based on the content type which best reflects the data which most users are searching for. For instance, people viewing substances are generally most interested in viewing diseases that these substances have shown to have positive influences. This section is for allowing more advanced sorting methods. Currently, these advanced sorting methods are available for members only. If you are already a member, you can sign in by clicking here. If you do not currently have a user account, and would like to create one/become a member, click here to begin the singup process ...
Liver Session Role of allo-antibodies in the development of progressive fibrosis in pediatric livery allografts and need for a unique grading system ...
Table of Contents. Table of Contents 2. List of Tables 7. List of Figures 8. Introduction 9. Global Markets Direct Report Coverage 9. Fibrosis Overview 10. Therapeutics Development 11. Pipeline Products for Fibrosis-Overview 11. Pipeline Products for Fibrosis-Comparative Analysis 12. Fibrosis-Therapeutics under Development by Companies 13. Fibrosis-Therapeutics under Investigation by Universities/Institutes 15. Fibrosis-Pipeline Products Glance 16. Clinical Stage Products 16. Early Stage Products 17. Unknown Stage Products 18. Fibrosis-Products under Development by Companies 19. Fibrosis-Products under Investigation by Universities/Institutes 21. Fibrosis-Companies Involved in Therapeutics Development 22. Abeome Corporation 22. Acceleron Pharma, Inc. 23. Complexa, Inc. 24. Digna Biotech, S.L. 25. F. Hoffmann-La Roche Ltd. 26. FibroGen, Inc. 27. GlycoMimetics, Inc. 28. HanAll Biopharma Co., Ltd. 29. Isarna Therapeutics GmbH 30. Lycera Corp. 31. miRagen Therapeutics, Inc. 32. Neumedicines Inc. ...
A team of scientists has developed a playbook for ending the devastating impact of fibrotic diseases of the liver, lung, kidney, and other organs, which are responsible for as many as 45 percent of all deaths in the industrialized ...
Evento no competitivo en el que la solidaridad, el compañerismo y las ganas de practicar la natación en las aguas de Formentera se unen para ayudar a los niños y jóvenes con Fibrosis Quística
Evento no competitivo en el que la solidaridad, el compañerismo y las ganas de practicar la natación en las aguas de Formentera se unen para ayudar a los niños y jóvenes con Fibrosis Quística
We are utilising the power of our i-body technology platform to develop a pipeline of i-bodies, with an initial focus on treating fibrotic diseases.
Fibrotic Diseases | Scientific research info incl meetings, conferences, seminars, symposia,tradeshows,jobs,jobfairs, professional tips and more.
These findings confirm percolation as a potential mechanism to explain AF in humans and give new insights into dynamics underlying conduction distortions and fractionated signals in excitable media, which correlate well with the experimental findings in fibrotic regions. The greater understanding of …
纤维化程度 在 消化系统疾病 分类中 的翻译结果:fibrosis;fibrosis degree;degree of fibrosis||双语例句|英文例句|相关文摘
Systemic sclerosis (SSc) is a connective tissue disorder characterised by the development of skin fibrosis. Our current understanding of the disease pathogenesis is incomplete and the study of SSc is hindered, at least partially, by a lack of animal models that fully replicate the complex state of human disease. Murine model of bleomycin-induced dermal fibrosis encapsulates important events that take place early in the disease course. To characterise the optimum in vivo parameters required for the successful induction of dermal fibrosis we subjected three commonly used mouse strains to repeated subcutaneous bleomycin injections. We aimed to identify the effects of genetic background and gender on the severity of skin fibrosis. We used male and female Balb/C, C57BL/6, and DBA/2 strains and assessed their susceptibility to bleomycin-induced fibrosis by measuring dermal thickness, hydroxyproline/collagen content and number of resident myofibroblasts, all of which are important indicators of the severity of
Adipose tissue fibrosis development blocks adipocyte hypertrophy and favors ectopic lipid accumulation. Here, we show that adipose tissue fibrosis is associated with obesity and insulin resistance in humans and mice. Kinetic studies in C3H mice fed a high-fat diet show activation of macrophages and progression of fibrosis along with adipocyte metabolic dysfunction and death. Adipose tissue fibrosis is attenuated by macrophage depletion. Impairment of Toll-like receptor 4 signaling protects mice from obesity-induced fibrosis. The presence of a functional Toll-like receptor 4 on adipose tissue hematopoietic cells is necessary for the initiation of adipose tissue fibrosis. Continuous low-dose infusion of the Toll-like receptor 4 ligand, lipopolysaccharide, promotes adipose tissue fibrosis. Ex vivo, lipopolysaccharide-mediated induction of fibrosis is prevented by antibodies against the profibrotic factor TGFβ1. Together, these results indicate that obesity and endotoxemia favor the development of adipose
Fibroproliferative disorders such as idiopathic pulmonary fibrosis and systemic sclerosis have no effective therapies and result in significant morbidity and mortality due to progressive organ fibrosis. We examined the effect of peptides derived from endostatin on existing fibrosis and fibrosis triggered by two potent mediators, transforming growth factor-β (TGF-β) and bleomycin, in human and mouse tissues in vitro, ex vivo, and in vivo. We identified one peptide, E4, with potent antifibrotic activity. E4 prevented TGF-β-induced dermal fibrosis in vivo in a mouse model, ex vivo in human skin, and in bleomycin-induced dermal and pulmonary fibrosis in vivo, demonstrating that E4 exerts potent antifibrotic effects. In addition, E4 significantly reduced existing fibrosis in these preclinical models. E4 amelioration of fibrosis was accompanied by reduced cell apoptosis and lower levels of lysyl oxidase, an enzyme that cross-links collagen, and Egr-1 (early growth response gene-1), a transcription ...
... progressive chronic kidney disease (CKD). suppressed the immunoreactivity of mTOR signaling, which decreased the inflammatory responses and ECM accumulation in the obstructed kidneys. Isolated macrophages from rapamycin-treated obstructed kidneys presented less inflammatory activity than vehicle groups. In vitro study confirmed that rapamycin significantly inhibited the fibrogenic activation of cultured fibroblasts (NIH3T3 cells), which was induced by the stimulation of TGF-1. Further experiment revealed that rapamycin did not directly inhibit the fibrogenesis of HK2 cells with aristolochic acid treatment. Our findings clarified that rapamycin can ameliorate kidney fibrosis by blocking the mTOR signaling in interstitial macrophages and myofibroblasts. Introduction Tubulointerstitial fibrosis is the final common pathway of a wide variety of chronic progressive kidney diseases. Intense studies have focused on the molecular and ...
TY - JOUR. T1 - Associations of electrocardiographic P-wave characteristics with left atrial function, and diffuse left ventricular fibrosis defined by cardiac magnetic resonance. T2 - The PRIMERI study. AU - Win, Theingi Tiffany. AU - Venkatesh, Bharath Ambale. AU - Volpe, Gustavo J.. AU - Mewton, Nathan. AU - Rizzi, Patricia. AU - Sharma, Ravi K.. AU - Strauss, David G.. AU - Lima, Joao A.. AU - Tereshchenko, Larisa G.. PY - 2015/1/1. Y1 - 2015/1/1. N2 - BACKGROUND: Abnormal P-terminal force in lead V1 (PTFV1) is associated with an increased risk of heart failure, stroke, atrial fibrillation, and death. OBJECTIVE: Our goal was to explore associations of left ventricular (LV) diffuse fibrosis with left atrial (LA) function and electrocardiographic (ECG) measures of LA electrical activity. METHODS: Patients without atrial fibrillation (n = 91; mean age 59.5 years; 61.5% men; 65.9% white) with structural heart disease (spatial QRS-T angle ≥105° and/or Selvester QRS score ≥5 on ECG) but LV ...
Background: Using cardiovascular magnetic resonance imaging (CMR), it is possible to detect diffuse fibrosis of the left ventricle (LV) in patients with atrial fibrillation (AF), which may be independently associated with recurrence of AF after ablation. By conducting CMR, clinical, electrophysiology and biomarker assessment we planned to investigate LV myocardial fibrosis in patients undergoing AF ablation. Methods: LV fibrosis was assessed by T1 mapping in 31 patients undergoing percutaneous ablation for AF. Galectin-3, coronary sinus type I collagen C terminal telopeptide (ICTP), and type III procollagen N terminal peptide were measured with ELISA. Comparison was made between groups above and below the median for LV extracellular volume fraction (ECV), followed by regression analysis. Results: On linear regression analysis LV ECV had significant associations with invasive left atrial pressure (Beta 0.49, P = 0.008) and coronary sinus ICTP (Beta 0.75, P , 0.001), which remained significant on ...
Renal fibrosis is characterized by activation and proliferation of fibroblasts, which continually produce and deposit ECM proteins, leading to progressive fibrosis. Herein we demonstrate that GSK3β is expressed in myofibroblasts, and GSK3β expression and activity are increased in mouse kidneys following I/R and in cultured fibroblasts following TGF-β1 treatment. Pharmacological inhibition of GSK3 using TDZD significantly reduced pro-inflammatory and pro-fibrotic cytokines, macrophage infiltration and ECM deposition, thereby reducing fibrosis. GSK3 inhibition reduced the myofibroblast population in vivo and fibroblast-to-myofibroblast differentiation in vitro by a TGF-β-SMAD signaling-dependent mechanism. Thus, GSK3β plays a pro-fibrotic role in the kidney following I/R, and its inhibition, even after the injury has occurred, could prevent the future development of fibrosis.. GSK3β is expressed in proximal tubules (Nørregaard et al., 2015), and increased GSK3β has been detected in renal ...
In the pathogenesis of renal fibrosis, oxidative stress (OS) enhances the production of reactive oxygen species (ROS) leading to sustained cell growth, inflammation, excessive tissue remodelling and accumulation, which results in the development and acceleration of renal damage. In our previous work (128) we established protein DJ-1 (PARK7) as an important ROS scavenger and key player in renal cell response to OS. In the present study we investigated the impact of profibrogenic agonists on DJ-1 and shed light on the role of this protein in renal fibrosis. Treatment of renal fibroblasts and epithelial cells with the profibrogenic agonist ANG II or PDGF resulted in a significant up-regulation of DJ-1 expression parallel to an increase in the expression of fibrosis markers. Monitoring of DJ-1 expression in kidney extract and tissue sections from renal fibrosis mice model (Col4a3-deficient) revealed a disease grad dependent regulation of the protein. Overexpression of DJ-1 prompted cell resistance ...
A total of 32 patients (36.4%) had hypertension, 21 (23.9%) with hyperlipidemia, 9 (10.2%) with diabetes, 6 (6.8%) patients had with a history of tobacco abuse and 10 (11.4%) with coronary artery disease. A total of 38 (43.2%) patients were on statin, 25 (28.4%) were on angiotensin converting enzyme inhibitor, 36 (40.9%) were on a beta-°©-blocker, 31 (35.2%) were on anticoagulant, and 13 (14.8%) were on antiarrhythmic medication. Subsequent follow-°©-up MRIs were performe on 32 (36%) patients that exhibited progression of atrial fibrosis.. Using univariate logistic regression models we were not able to identify significant predictors of fibrosis progression. The majority of patients (64%) did not reveal any significant changes from the initial quality and quantity of atrial fibrosis at 1 year MRI follow-up. ...
The objective of our study was to investigate the effect of Aliskiren, a renin inhibitor, on the deoxycorticosterone (DOCA) induced myocardial fibrosis in a rat model and its underlying mechanism. A total of 45 Sprague-Dawley (SD) rats underwent right nephrectomy and were randomly assigned into 3 groups: control group (CON group: silicone tube was embedded subcutaneously); DOCA treated group (DOC group: 200 mg of DOCA was subcutaneously administered); DOCA and Aliskiren (ALI) treated group (ALI group: 200 mg of DOCA and 50 mg/kg/d ALI were subcutaneously and intragastrically given, respectively). Treatment was done for 4 weeks. Sirius red staining was employed to detect the expression of myocardial collagen, and the myocardial collagen volume fraction (CVF) and perivascular collagen volume area (PVCA) were calculated. Radioimmunoassay was carried out to measure the renin activity (RA) and content of angiotensin II (Ang II) in the plasma and ventricle. Western blot assay was done to detect the ...
The objective of our study was to investigate the effect of Aliskiren, a renin inhibitor, on the deoxycorticosterone (DOCA) induced myocardial fibrosis in a rat model and its underlying mechanism. A total of 45 Sprague-Dawley (SD) rats underwent right nephrectomy and were randomly assigned into 3 groups: control group (CON group: silicone tube was embedded subcutaneously); DOCA treated group (DOC group: 200 mg of DOCA was subcutaneously administered); DOCA and Aliskiren (ALI) treated group (ALI group: 200 mg of DOCA and 50 mg/kg/d ALI were subcutaneously and intragastrically given, respectively). Treatment was done for 4 weeks. Sirius red staining was employed to detect the expression of myocardial collagen, and the myocardial collagen volume fraction (CVF) and perivascular collagen volume area (PVCA) were calculated. Radioimmunoassay was carried out to measure the renin activity (RA) and content of angiotensin II (Ang II) in the plasma and ventricle. Western blot assay was done to detect the ...
Cysteine-rich protein 61 (Cyr61) is a secreted matrix-associated protein that regulates a broad spectrum of biological and cellular activities. This study aimed to investigate the role of Cyr61 in progressive kidney fibrosis induced by unilateral ureteral obstruction (UUO) surgery in mice. The expression of Cyr61 transcripts and proteins in the obstructed kidneys were increased from day 1 and remained high until day 10 after surgery. Immunohistochemistry indicated that Cyr61 was expressed mainly in renal tubular epithelial cells. The upregulated Cyr61 in UUO kidneys was reduced in mice treated with pan-transforming growth factor-β (TGF-β) antibody. The role of TGF-β in tubular Cyr61 upregulation after obstructive kidney injury was further supported by experiments showing that TGF-β1 stimulated Cyr61 expression in cultured tubular epithelial cells. Notably, the upregulation of Cyr61 in UUO kidneys was followed by a marked increase in monocyte chemoattractant protein 1 (MCP-1) ...
Finding a gene for familial cardiac fibrosis (NHS grant 2000.130) Summary of results. A large multi-generation family with an autosomal dominantly inherited form of cardiac fibrosis with a highly malignant clinical outcome is presented and used to identify the gene causing this disease. We consider it a hereditary form of cardiac fibrosis since it was shown that the myocardial fibrosis in this family preceded the clinical and echocardiographic signs.. Twenty-four individuals from this family were clinically evaluated and 18 of them were used for a genome wide linkage analysis giving the highest LOD score (2.6) in the region of the lamin AC (LMNA) gene. Mutation analyses of this candidate gene failed to show a point mutation. Subsequent Southern blot and multiplex ligation-dependent probe amplification analyses, however, revealed a deletion of the start-codon containing exon. The up- and downstream flanking exons proved not to be deleted.. Furthermore, we demonstrate in-vitro that the deletion ...
The master cytokine TGF-β mediates tissue fibrosis associated with inflammation and tissue injury. TGF-β induces fibroblast activation and differentiation into myofibroblasts that secrete extracellular matrix proteins. Canonical TGF-β signaling mobilizes Smad2 and Smad3 transcription factors that control fibrosis by promoting gene expression. However, the importance of TGF-β-Smad2/3 signaling in fibroblast-mediated cardiac fibrosis has not been directly evaluated in vivo. Here, we examined pressure overload-induced cardiac fibrosis in fibroblast- and myofibroblast-specific inducible Cre-expressing mouse lines with selective deletion of the TGF-β receptors Tgfbr1/2, Smad2, or Smad3. Fibroblast-specific deletion of Tgfbr1/2 or Smad3, but not Smad2, markedly reduced the pressure overload-induced fibrotic response as well as fibrosis mediated by a heart-specific, latency-resistant TGF-β mutant transgene. Interestingly, cardiac fibroblast-specific deletion of Tgfbr1/2, but not Smad2/3, ...
2015 The Authors. Uncontrolled extracellular matrix (ECM) production by fibroblasts in response to injury contributes to fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Reactive oxygen species (ROS) generation is involved in the pathogenesis of IPF. Transforming growth factor-β1 (TGF-β1) stimulates the production of NADPH oxidase 4 (NOX4)-dependent ROS, promoting lung fibrosis (LF). Dysregulation of microRNAs (miRNAs) has been shown to contribute to LF. To identify miRNAs involved in redox regulation relevant for IPF, we performed arrays in human lung fibroblasts exposed to ROS. miR-9-5p was selected as the best candidate and we demonstrate its inhibitory effect on TGF-β receptor type II (TGFBR2) and NOX4 expression. Increased expression of miR-9-5p abrogates TGF-β1-dependent myofibroblast phenotypic transformation. In the mouse model of bleomycin-induced LF, miR-9-5p dramatically reduces fibrogenesis and inhibition of miR-9-5p and prevents its anti-fibrotic effect both in ...
The biology of heart failure is complex and diverse (2), posing challenges for developing efficacious therapies. All but one recent phase III heart failure trial failed to reduce mortality (3). Unlike oncology, we do not split heart failure into subtypes on the basis of disease pathways (4). We need a more targeted approach, not only for drug development, but also for drug response monitoring. Myocardial fibrosis is an attractive biomarker-fibrosis is already an established marker in the liver, kidneys, and lung-and likely a causal disease pathway mediating outcomes. Cardiac fibrosis can be measured on myocardial biopsy and tracks disease severity and outcome (5,6). But biopsy is invasive and impractical for routine clinical diagnosis and monitoring (7). Many of our current measurements are partial surrogates for fibrosis (e.g., imaging for cardiac remodeling, systolic and diastolic function), but more are needed, particularly circulating blood biomarkers. Cardiology quantifies only 2 myocardial ...
TY - JOUR. T1 - A DDX5 S480A polymorphism is associated with increased transcription of fibrogenic genes in hepatic stellate cells. AU - Guo, Jinsheng. AU - Hong, Feng. AU - Loke, Johnny. AU - Yea, Steven. AU - Lim, Chooi Ling. AU - Lee, Ursula. AU - Mann, Derek A.. AU - Walsh, Martin J.. AU - Sninsky, John J.. AU - Friedman, Scott L.. PY - 2010/2/19. Y1 - 2010/2/19. N2 - We recently identified a missense single nucleotide polymorphism (SNP) in DDX5 (rs1140409, p.S480A) that enhances the risk of developing cirrhosis. DDX5 is an ATP-dependent RNA helicase and transcriptional modulator. We hypothesized that the activity of DDX5 in regulating fibrogenic gene transcription in hepatic stellate cells (HSCs) is altered by the S480A SNP. To test this, we employed two approaches: 1) transient overexpression of DDX5 cDNA or siRNA knockdown of endogenous DDX5, with replacement by either DDX5 wild type (WT) or SNP cDNA, or 2) stable expression of exogenous DDX5 WT and SNP in HSC lines. WT DDX5 mRNA in HSCs ...
Renal tubular atrophy and interstitial fibrosis are common hallmarks of etiologically different progressive chronic kidney diseases (CKD) that eventually result in organ failure. Even though these pathological manifestations constitute a major public health problem, diagnostic tests, as well as therapeutic options, are currently limited. Members of the dickkopf (DKK) family, DKK1 and -2, have been associated with inhibition of Wnt signaling and organ fibrosis. Here, we identify DKK3 as a stress-induced, tubular epithelia-derived, secreted glycoprotein that mediates kidney fibrosis. Genetic as well as antibody-mediated abrogation of DKK3 led to reduced tubular atrophy and decreased interstitial matrix accumulation in two mouse models of renal fibrosis. This was facilitated by an amplified, antifibrogenic, inflammatory T cell response and diminished canonical Wnt/β-catenin signaling in stressed tubular epithelial cells. Moreover, in humans, urinary DKK3 levels specifically correlated with the ...
Results Females in all three groups had significantly increased septal myocardial ECV compared with males (0.29±0.03 vs 0.25±0.03, p,0.01). Septal myocardial ECV was higher in ALMS than hypertensive and controls (0.28±0.02 vs 0.25±0.03 vs 0.24±0.03, p,0.05). Three male older ALMS patients (mean 43±5 years vs 27±10 years) without a history of infantile CM had patchy diffuse LE in non-coronary artery territories with an increased ECV compared to remote normal myocardium (ECV 0.41±0.08 vs 0.27±0.03, p,0.05). MAPSE was reduced in patients with ALMS and hypertension compared to controls (13±2 cm/s vs 12±3 cm/s vs 17±2 cm/s, p,0.01. There were no differences in LV ejection fraction, LV mass or LA volumes. Septal myocardial ECV was negatively correlated with a MAPSE in patients with ALMS (r=−0.64, p,0.05). NT-BNP was not correlated with septal ECV but was increased in patients with LGE (median 178 pmol/l vs 44 pmol/l).. ...