scholarly journals Role of Lipoprotein (a) and TGF-β1 in Atherosclerosis of Hemodialysis Patients

2000 ◽  
Vol 11 (10) ◽  
pp. 1889-1895
Author(s):  
MASAHISA FUJISAWA ◽  
REIKO HARAMAKI ◽  
HIROSHI MIYAZAKI ◽  
TSUTOMU IMAIZUMI ◽  
SEIYA OKUDA

Abstract. Atherosclerotic vascular disease is a major cause of death for uremic patients who are on hemodialysis (HD). Recent evidence suggests that lipoprotein (a) [Lp(a)] may aggravate atherosclerosis by inhibiting activation of transforming growth factor-β1 (TGF-β1). Plasma Lp(a) and plasma TGF-β1 activation in HD patients (n = 51), chronic renal failure patients not subjected to hemodialysis (non-HD-CRF; n = 12), and healthy volunteers (control; n = 13) were investigated. Plasma Lp(a) was significantly higher in HD (18.75 ± 1.62 mg/ml) and non-HD-CRF patients (25.0 ± 8.4 mg/ml) than in control subjects (10.9 ± 5.8 mg/ml). The degree of atherosclerosis in HD patients was assessed by measuring the intima-media thickness (IMT) and plaque score with the use of an ultrasound scanner. IMT and plaque score were higher in HD and non-HD-CRF patients than in controls. A significant positive correlation was found in HD patients between Lp(a) and IMT (r = 0.377, P < 0.01) as well as between Lp(a) and plaque score (r = 0.43, P < 0.01). Plasma total TGF-β1 significantly increased in HD (119.8 ± 53.5 ng/ml) and non-HD-CRF patients (93.2 ± 25.0 ng/ml) compared with control subjects (17.7 ± 6.4 ng/ml), whereas the plasma level of mature (active) TGF-β1 did not differ among the groups. When plasma TGF-β1 and supernatant TGF-β1 from cultured peripheral mononuclear cells were compared before and after an HD session, neither total nor mature TGF-β1 showed a significant difference between the values before and after an HD session. There were no significant relationships between plasma total TGF-β1 and IMT or plaque score, between mature TGF-β1 and IMT or plaque score, or between mature TGF-β1 and Lp(a). In conclusion, Lp(a) may be an important atherogenic factor in CRF patients. However, it was not clarified whether Lp(a) exerts its effect by inhibiting TGF-β1 activation in CRF patients.

1974 ◽  
Vol 77 (2) ◽  
pp. 401-407 ◽  
Author(s):  
J. A. Mahoudeau ◽  
A. Delassalle ◽  
H. Bricaire

ABSTRACT Plasma levels of testosterone (T) and 5α-dihydrotestosterone (DHT) were determined by radioimmunoassay in 29 patients with benign prostatic hypertrophy (BPH) and in 56 control men of various ages. No significant difference was found in T, DHT nor DHT/T ratio between BPH and control subjects of similar age. Plasma DHT was higher in the prostatic than in the peripheral veins in 8/9 patients with BPH during laparotomy, indicating a prostatic secretion of DHT. No difference in the mean T nor the mean DHT was found in peripheral plasma before and after adenomectomy.


Cardiology ◽  
2015 ◽  
Vol 131 (2) ◽  
pp. 97-106 ◽  
Author(s):  
Weili Qiao ◽  
Cheng Wang ◽  
Bing Chen ◽  
Fan Zhang ◽  
Yaowu Liu ◽  
...  

Objective: To investigate the effects of ibuprofen on cardiac fibrosis in a rat model of type 1 diabetes. Methods: The diabetic model was established by injecting streptozotocin into the rats. Then, ibuprofen or pioglitazone was given by gavage for 8 weeks. The cardiac fibrosis was assessed, and the major components of the renin-angiotensin system, the transforming growth factor β1 (TGF-β1) and the mammalian target of rapamycin (mTOR), were evaluated by histopathological, immunohistochemical, Western blot analysis or ELISA assay. Results: Obvious cardiac fibrosis was detected in the diabetic group and was alleviated by ibuprofen treatment. Angiotensin-converting enzyme (ACE), angiotensin (Ang) II and AngII type 1 receptor (AT1-R) levels were higher, and ACE2, Ang(1-7) and Mas receptor (Mas-R) were lower in the diabetic group. The ratio of ACE to ACE2 was raised in the diabetic group. All these changes were ameliorated by ibuprofen. TGF-β1 and mTOR were raised in the hearts of the diabetic group and were attenuated by ibuprofen treatment. There was no significant difference between the ibuprofen and the pioglitazone groups. Conclusion: Ibuprofen could ameliorate the cardiac fibrosis in diabetic rats by reduction of the ACE/AngII/AT1-R axis and enhancement of the ACE2/Ang(1-7)/Mas-R axis, leading to a decrease in TGF-β1 and mTOR.


2019 ◽  
Vol 47 (4) ◽  
pp. 470-477
Author(s):  
Hany Aly ◽  
Yasmeen Mansi ◽  
Zahraa Ez El Din ◽  
Hala Gabr Metwally ◽  
Amira Sabry

Abstract Background The pathogenesis of bronchopulmonary dysplasia (BPD) includes arrest of alveolar septation and enhanced fibrosis. We hypothesized that mesenchymal stromal cells (MSC) and transforming growth factor-β1 (TGF-β1) in tracheal aspirates of mechanically ventilated premature infants differ in BPD and non-BPD infants. Methods Tracheal aspirates were collected during the first week of life. Mononuclear cells were separated, cultured and immunophenotyped by flow cytometry. MSCs colony/cluster ratio was calculated as an index for dysplastic potentials. TGF-β1 was assessed by enzyme-linked immunosorbent assay (ELISA). Setting: Neonatal intensive care unit. Patients Premature infants at risk for BPD. Results A total of 121 preterm infants were enrolled; 27 of them died and among the 94 survivors 23 infants had BPD. MSCs were identified in younger [gestational age (GA): 30.9±1.7 vs. 31.8±1.8, P=0.025] and smaller [birth weight (BW): 1.3±0.28 vs. 1.44±0.37 kg, P=0.04] infants with lower Apgar scores. The recovery rate of MSCs in BPD and non-BPD groups did not differ. BPD group had significantly smaller colony/cluster ratio compared to non-BPD (0.97 vs. 4.25, P=0.002). TGF-β1 was significantly greater in BPD infants (4173.9±864.3 vs. 3705.8±540.5 pg/mL, P=0.021). Conclusion Infants with BPD had different MSCs morphology and greater TGF-β1 expression. The pathogenesis for these morphological changes of resident lung MSCs needs further studying.


2005 ◽  
Vol 73 (9) ◽  
pp. 5908-5914 ◽  
Author(s):  
A. Kariminia ◽  
E. Bourreau ◽  
H. Pascalis ◽  
P. Couppié ◽  
D. Sainte-Marie ◽  
...  

ABSTRACT Transforming growth factor β (TGF-β) has been shown to be a central immunomodulator used by leishmaniae to escape effective mechanisms of protection in human and murine infections with these parasites. However, all the information is derived from studies of established infection, while little is known about TGF-β production in response to Leishmania stimulation in healthy subjects. In this study, TGF-β1 production was demonstrated in peripheral blood mononuclear cells from healthy subjects never exposed to leishmaniae in response to live Leishmania guyanensis, and the TGF-β1-producing cells were described as a distinct subpopulation of CD4+ CD25+ regulatory T cells. The suppressive properties of CD4+ CD25+ T cells were demonstrated in vitro by their inhibition of production of interleukin 2 (IL-2) and IL-10 by CD4+ CD25− T cells in the presence of either anti-CD3 or L. guyanensis. Although neutralization of TGF-β1 did not reverse the suppressive activity of CD4+ CD25+ T cells activated by anti-CD3, it reversed the suppressive activity of CD4+ CD25+ T cells activated by L. guyanensis. Altogether our data demonstrated that TGF-β1 is involved in the suppressive activity of L. guyanensis-stimulated CD4+ CD25+ T cells from healthy controls.


Cephalalgia ◽  
2009 ◽  
Vol 29 (3) ◽  
pp. 365-372 ◽  
Author(s):  
SH Bø ◽  
EM Davidsen ◽  
P Gulbrandsen ◽  
E Dietrichs ◽  
G Bovim ◽  
...  

Cytokines have been measured in cerebrospinal fluid (CSF) from headache patients [infrequent episodic tension-type headache (TTH) and migraine with or without aura, all during attack, and cervicogenic headache] and compared with levels in pain-free individuals. Both proinflammatory [interleukin (IL)-1β, tumour necrosis factor-α and monocyte chemoattractant protein-1 (MCP-1)] and anti-inflammatory cytokines IL-1 receptor antagonist (IL-1ra), IL-4, IL-10 and transforming growth factor-β1 (TGF-β1)] were included. There were significant group differences in IL-1ra, TGF-β1 and MCP-1 in episodic TTH and migraine compared with controls, and a significant difference in MCP-1 between cervicogenic headache and migraine with aura. Intrathecal MCP-1 correlated with IL-1ra, IL-10 and TGF-β1 in episodic TTH, and MCP-1 with IL-10 in migraine with aura. Cytokine increases were modest compared with those often accompanying serious neurological conditions, and may represent a mild response to pain. We believe this to be the first comparative study of CSF cytokine levels in connection with headache.


1970 ◽  
Vol 15 (2) ◽  
Author(s):  
Rachmat Budi Prasetyo ◽  
Soetojo Soetojo ◽  
Doddy M Soebadi

Objective: To compare the PSA and TGF-β1 plasma level before and after administration of a 5α-reductase inhibitor (dutasteride) and an anti estrogen (tamoxifen) in nonobstructive patients with BPH. Material and Method: We enrolled 40 patients with a diagnosis of BPH without urinary retention. Patients were allocated into 4 groups of 10 patients and were given tamoxifen, dutasteride, a combination of tamoxifen and dutasteride, or placebo. We measured PSA and TGF-β1 plasma levels at study entry and 3 months after administration. Data were analysed using SPSS 12. Results: Increase of TGF-β1, as high as 54% (2,18 ± 0,88 to 3,36 ± 1,06) in the tamoxifen group, 26% (2,75 ± 0,62 to 3,47 ± 0,82) in the dutasteride group, and 92% (2,37 ± 0,75 to 4,56 ± 1,98) in the combination group, was significant (p < 0,05). PSA was not significantly decreased in all groups (p > 0,05). PSA decreased 28% (4,25 ± 3,28 to 3,06 ± 3,08) in the tamoxifen group, 27% (2,20 ± 2,17 to 1,60 ± 0, 982) in the dutasteride group, and 19% (2,95 ± 1,22 to 2,40 ± 1,78) in the combination group. In the placebo group was no significant difference of both parameters. Conclusion: TGF-β1 was significantly increased in all groups except in placebo. PSA was decreased in all groups but not significant statistically. We concluded that TGF-β1 may better be used as a biomarker in the evaluation and management of BPH than PSA.


Author(s):  
Edna Ayerim Mandujano-Tinoco ◽  
Francisco González-García ◽  
Rosa M Salgado ◽  
René Fernando Abarca-Buis ◽  
José Manuel Sanchez-Lopez ◽  
...  

Abstract Grafting is the gold standard for the treatment of severe skin burns. Frequently, allogeneic tissue is the only transient option for wound coverage, but their use risks damage to surrounding tissues. MicroRNAs have been associated with acute rejection of different tissues/organs. In this study, we analyzed the expression of miR-31, miR-155, and miR-221 and associate it with graft tolerance or rejection using a murine full-thickness skin transplantation model. Recipient animals for the syngeneic and allogeneic groups were BALB/c and C57BL/6 mice, respectively; donor tissues were obtained from BALB/c mice. After 7 days post-transplantation (DPT), the recipient skin and grafts in the syngeneic group maintained most of their structural characteristics and transforming growth factor (TGF)β1 and TGFβ3 expression. Allografts were rejected early (Banff grades II and IV at 3 and 7 DPT, respectively), showing damage to the skin architecture and alteration of TGFβ3 distribution. miRNAs skin expression changed in both mouse strains; miR-31 expression increased in the recipient skin of syngeneic grafts relative to that of allogeneic grafts at 3 and 7 DPT (p &lt; 0.05 and p &lt; 0.01, respectively); miR-221 expression increased in the same grafts at 7 DPT (p &lt; 0.05). The only significant difference between donor tissues was observed for miR-155 expression at 7 DPT which was associated with necrotic tissue. Only miR-31 and miR-221 levels were increased in the blood of BALB/c mice that received syngeneic grafts after 7 DPT. Our data suggest that local and systemic miR-31 and miR-221 overexpression are associated with graft tolerance.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3920-3920
Author(s):  
Yun Ling ◽  
Xiangshan Cao ◽  
Ziqiang Yu ◽  
Changgeng Ruan

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune disorder and high-dose dexamethasone (HD-DXM) has been used as a first-line therapy for patients with ITP. However, little is known about the role of CD4+CD25 + regulatory T (Treg) cells, interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1) in the pathogenesis of chronic ITP and the effects of HD-DXM on them contained Treg cells, IL-10 and TGF-β1. In this study, we investigated the expressions of Treg cells, IL-10 and TGF-β1 in 26 untreated adult patients with chronic ITP. All patients had thrombocytopenia (platelet count &lt;50 × 109/L) for more than 6 months. We also observed short time changes of Treg cells, IL-10 and TGF-β1 after treatment with HD-DXM in these patients. The results showed that a good initial response to HD-DXM occurred in 24 of the 26 patients with chronic ITP (92.3%): the mean platelet count was (84.9±30.4)×109/L [range, (20∼150) ×109/L] one week after the initiation of treatment. The proportion of CD4+CD25+ T cells in the peripheral blood of patients with chronic ITP was significantly higher than that in normal controls(P&lt;0.001); there was no significant difference in the percentage of CD4+CD25high T cells between patients and controls ( P=0.317); but the number of CD4+ FOXP3+ T cells in patients was significantly lower than that in controls (P&lt;0.001). After 4-days treatment with HD-DXM, the numbers of CD4+ CD25+ T cells (P&lt;0.001), CD4+CD25high T cells ( P&lt;0.001), and CD4+FOXP3+ T cells ( P&lt;0.001) in patients were all significantly increased. In the serum of chronic ITP patients, the expression level of TGF-β1 was lower than that of healthy controls (P&lt;0.0001) and HD-DXM could significantly increase it; there was no significant difference in the expression level of IL-10 between patients and controls ( P&gt;0.05) and there was no remarkable change of IL-10 in patients after HD-DXM treatment (P&gt;0.05). The mRNA levels of Foxp3 and TGF-β1 gene in patients were lower than those of controls (P&lt;0.05 and P&lt;0.05); HD-DXM administration significantly increased the expressions of Foxp3 and TGF-β1 gene(P&lt;0.05 and P&lt;0.0001), which were even higher than those of controls(P&lt;0.05 and P&lt;0.05); There was a positive correlation between the Foxp3 mRNA expression and TGF-β1 after treatment with HD-DXM (r =0.403, P=0.041). These results suggest that Foxp3 and TGF-β1 gene are deficient in chronic ITP and the immunosuppressive therapy of glucocorticoids could improve the expression levels of these genes.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Hui Du ◽  
Yonghong Wang ◽  
Yumin Shi ◽  
Jian Yu ◽  
Wen Sun ◽  
...  

Objective. To observe the effects of empirical prescriptions of traditional Chinese medicine (TCM) on inflammatory mediators in pediatric asthma and to explore the underlying molecular mechanism in the treatment of asthma.Methods. A total of 182 children with asthma were randomly placed into either the TCM group (n=97) or the salbutamol and montelukast (SM) group (n=85). Patients in the TCM group were treated with a series of empirical prescriptions of TCM, while those in the SM group received salbutamol and montelukast. Both groups received their respective treatment for 12 weeks. There were 35 patients in TCM group and 34 patients in SM group providing venous blood. Real-time PCR was used to determine the mRNA expression levels of interleukin- (IL-) 10, IL-17, matrix metalloproteinase-9 (MMP-9), and transforming growth factorβ1 (TGF-β1) in peripheral blood mononuclear cells before and after treatment. Enzyme-linked immunosorbent assay was used to measure the levels of IL-10, IL-17, MMP-9, and TGF-β1 in peripheral blood before and after treatment.Results. The mRNA expression of TGF-β1 in the SM group was downregulated (P=0.00) after treatment. No significant differences were found between the TCM group and the SM group after treatment (P>0.05). In the TCM group, the levels of IL-10, IL-17, and MMP-9 significantly decreased after treatment (P=0.01, 0.04, and 0.03, resp.). In the SM group, IL-17, MMP-9, and TGF-β1 levels significantly decreased after treatment (P=0.00, 0.03, and 0.00, resp.). There was no significant difference between the two groups regarding the levels of IL-10, IL-17, TGF-β1, and MMP-9 (P>0.05). The difference of the level of IL-17 was negatively correlated with the change of C-ACT score in TCM group and SM group.Conclusion. TCM has a regulatory effect on the balance of some inflammatory mediators in pediatric asthma.


2005 ◽  
Vol 289 (1) ◽  
pp. G116-G128 ◽  
Author(s):  
Bruce A. Vallance ◽  
M. Imelda Gunawan ◽  
Bryan Hewlett ◽  
Premysl Bercik ◽  
Corinne Van Kampen ◽  
...  

Crohn's disease (CD) is a chronic, relapsing inflammatory bowel disease, characterized by transmural inflammation. In CD, the recurrent inflammatory injury and tissue repair that occurs in the intestine can progress uncontrollably, leading to the proliferation of mesenchymal cells as well as fibrosis, characterized by excessive extracellular matrix deposition. These processes thicken the bowel wall, reducing flexibility, and often culminate in obstructive strictures. Because no effective measures are currently available to specifically treat or prevent intestinal stricturing, we sought to gain a better understanding of its pathogenesis by developing a mouse model of intestinal fibrosis. Because transforming growth factor (TGF)-β1 can mediate both fibrosis and mesenchymal cell proliferation; we studied the effects of delivering adenoviral vectors encoding spontaneously active TGF-β1 into the colons of mice. We first demonstrated that enema delivery of marker adenoviral vectors led to the transfection of the colonic epithelium and transient transgene expression. Histologically, control vectors caused an acute inflammatory response, involving the recruitment of neutrophils and mononuclear cells into the colonic lamina propria; however, infection caused little if any fibrosis. In contrast, the TGF-β1 vector caused a more severe and prolonged inflammatory response as well as localized collagen deposition, leading to severe and progressive fibrosis. This was accompanied by the emergence of cells with a myofibroblast phenotype. Ultimately the fibrosis resulted in many of the TGF-β1-transfected mice developing profound colonic obstruction. Through adenoviral gene transfer technology, we describe a novel mouse model of colitis and implicate TGF-β1 in the pathogenesis of obstructive intestinal fibrosis.


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