Age-dependent defective TGF-beta1 signaling in patients undergoing coronary artery bypass grafting

Redondo, Santiago; Navarro‐Dorado, Jorge; Ramajo, Marta; Medina, Úrsula; Molina-Sánchez, Pedro; Garcés, Z.; García-Alonso, Mauricio; Reguillo, Fernando del Rey; Rodrı́guez, Enrique; Andrés, Vicente; Tejerina, Teresa

doi:10.1186/1749-8090-9-24

Cited by 7 publications

(8 citation statements)

References 25 publications

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“…Some studies have reported an association between elevated TGF- β 1 levels and vascular restenosis lesions [ 30 , 44 ]. In contrast, other authors have showed that decreased expression of TGF- β 1 contributes to progression of atherosclerosis [ 10 , 22 , 23 ]. Nevertheless, the absence of the antiproliferative effects of TGF- β 1 in the blood vessels leads to increased chemotaxis, deposition of extracellular matrix, proliferation of vascular smooth muscle cells, and decreased apoptosis, thereby facilitating progression of atherosclerosis [ 45 , 46 ].…”

Section: Discussionmentioning

confidence: 91%

“…In turn, this leads to reduction of inflammatory cytokine-induced vascular cell adhesion molecule-1 (VCAM-1), chemotaxis, leucocyte adhesion to vascular endothelial lining, and decreased macrophage activity [ 19 , 21 ]. Previous studies have suggested that low serum levels of TGF- β 1 are a risk factor for atherosclerosis in non-CKD [ 22 , 23 ] and CKD patients [ 10 ]. However, there is a paucity of data on whether TGF- β 2 and TGF- β 3 contribute to the susceptibility and the severity of atherosclerosis in CKD patients.…”

Section: Introductionmentioning

confidence: 99%

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Transforming Growth Factor-β Protects against Inflammation-Related Atherosclerosis in South African CKD Patients

Hassan

Duarte

Dix-Peek

et al. 2018

International Journal of Nephrology

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Background Transforming growth factor-β (TGF-β) may inhibit the development of atherosclerosis. We evaluated serum levels of TGF-β isoforms concurrently with serum levels of endotoxin and various inflammatory markers. In addition, we determined if any association exists between polymorphisms in the TGF-β1 gene and atherosclerosis in South African CKD patients. Methods We studied 120 CKD patients and 40 healthy controls. Serum TGF-β1, TGF-β2, TGF-β3, endotoxin, and inflammatory markers were measured. Functional polymorphisms in the TGF-β1 genes were genotyped using a polymerase chain reaction-sequence specific primer method and carotid intima media thickness (CIMT) was assessed by B-mode ultrasonography. Results TGF-β isoforms levels were significantly lower in the patients with atherosclerosis compared to patients without atherosclerosis (p<0.001). Overall, TGF-β isoforms had inverse relationships with CIMT. TGF-β1 and TGF-β2 levels were significantly lower in patients with carotid plaque compared to those without carotid plaque [TGF-β1: 31.9 (17.2 – 42.2) versus 45.9 (35.4 – 58.1) ng/ml, p=0.016; and TGF-β2: 1.46 (1.30 – 1.57) versus 1.70 (1.50 – 1.87) ng/ml, p=0.013]. In multiple logistic regression, age, TGF-β2, and TGF-β3 were the only independent predictors of subclinical atherosclerosis in CKD patients [age: odds ratio (OR), 1.054; 95% confidence interval (CI): 1.003 – 1.109, p=0.039; TGF-β2: OR, 0.996; 95% CI: 0.994–0.999, p=0.018; TGF-β3: OR, 0.992; 95% CI: 0.985–0.999, p=0.029). TGF-β1 genotypes did not influence serum levels of TGF-β1 and no association was found between the TGF-β1 gene polymorphisms and atherosclerosis risk. Conclusion TGF-β isoforms seem to offer protection against the development of atherosclerosis among South African CKD patients.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Transforming Growth Factor-β Protects against Inflammation-Related Atherosclerosis in South African CKD Patients

Hassan

Duarte

Dix-Peek

et al. 2018

International Journal of Nephrology

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“…Thus, in humans with atherosclerosis, decreased TGF-β 1 signaling and loss of p27 expression could be found [25] . Attenuated TGF-β 1 signaling and expressions might be an attribution of vascular aging caused by atherosclerosis [26] .…”

Section: Discussionmentioning

confidence: 99%

Expressions of Transforming Growth Factor β1 Signaling Cytokines in Aortic Dissection

Yuan¹,

Lin²

2018

Braz J Cardiovasc Surg

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ObjectiveTo demonstrate the underlying mechanisms of aortic dissection compared to those of coronary artery disease in terms of the transforming growth factor-beta (TGF-β) signaling pathway.MethodsTwenty consecutive aortic dissection patients and 20 consecutive coronary artery disease patients undergoing a surgical treatment in this hospital were enrolled into this study. The aortic tissues were sampled and the TGF-β1 and its receptor TGF-β receptor I (TβRI) were detected by Western blotting assay.ResultsTGF-β1 and TβRI were positively expressed in the aortic tissues in both groups by Western blotting assay. The expressions of the two proteins were significantly higher in the aortic tissue of patients with aortic dissection than in those with coronary artery disease. The quantitative analyses of the relative gray scales of the proteins disclosed close correlations between the expressions of TGF-β1 and TβRI in both the study and control group patients.ConclusionsThe aortic remodeling of aortic dissection might differ from that of coronary artery atherosclerosis concerning the nature, mechanism, mode, and activities of TGF-β signaling pathway. The development of aortic dissection could be associated with a significantly enhanced function of TGF-β1/Smad signaling transduction as a result of aortic remodeling incorporating both vascular injury and repair.

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“…Recently, reduced TGFβ1 signaling with aging was shown in VSMCs ( 32 , 34 ). We thought that aging or other factors that affect TGFβ1 signaling may be responsible for the progression of disease, and the inhibition effect of TGFβ1 on ADAMTS4 expression may reduce and progress the disease.…”

Section: Discussionmentioning

confidence: 99%

A novel association between TGFb1 and ADAMTS4 in coronary artery disease: A new potential mechanism in the progression of atherosclerosis and diabetes

Uluçay

Çam²,

Batır³

et al. 2015

Anatol J Cardiol

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Objective:Coronary artery disease is characterized by atherosclerosis in the vessel wall. Recently, it has been thought that increasing LDL-binding capacity of subendothelial proteoglycan fragments that are formed by protease activity can be responsible for the initiation of atherosclerosis. ADAMTS4 is a member of the versican-degrading proteinases. In vitro studies demonstrated that TGFβ inhibits the expression of ADAMTS4 in macrophages. In this study, we aimed to investigate the role and association between TGFβ1 and ADAMTS4 in coronary artery disease.Methods:A total of 84 cases with atheroma plaque and 72 controls without plaque were analyzed. The severity of disease was determined by Gensini score. TGFβ1 gene polymorphisms were genotyped by the PCR-RFLP method. TGFβ1 and ADAMTS4 serum levels were measured by ELISA method. Statistical analyses of genotypes and their relationship with serum levels were performed by chi-square, student t test and ANOVA.Results:ADAMTS4 levels were higher in cases compared with controls (p<0.05). In the patient group, ADAMTS4 levels were higher than in controls and correlated with TGFβ1 serum levels (r=0.29; p<0.05) and severity of disease (r=0.20; p<0.05). The TGFβ1 gene CCA haplotype was associated with 3.3-fold increase in coronary artery disease (OR=3.26 95% CI 1.22-8.68; p<0.05). Unexpectedly, ADAMTS4 serum levels were also higher in diabetic cases (p=0.05).Conclusion:This study has demonstrated that ADAMTS4 may be responsible for the pathogenesis of atherosclerosis. This is the first report about the association between ADAMTS4 and TGFβ1 serum levels in the progression of atherosclerosis in CAD. Furthermore, it is seen that TGFβ1 haplotype can cause a genetic susceptibility to CAD in the Turkish population. To our knowledge, this is also the first report suggesting higher serum ADAMTS4 levels in diabetic patients.

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Age-dependent defective TGF-beta1 signaling in patients undergoing coronary artery bypass grafting

Cited by 7 publications

References 25 publications

Transforming Growth Factor-β Protects against Inflammation-Related Atherosclerosis in South African CKD Patients

Transforming Growth Factor-β Protects against Inflammation-Related Atherosclerosis in South African CKD Patients

Expressions of Transforming Growth Factor β1 Signaling Cytokines in Aortic Dissection

A novel association between TGFb1 and ADAMTS4 in coronary artery disease: A new potential mechanism in the progression of atherosclerosis and diabetes

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