Platelet expression of transforming growth factor beta 1 is enhanced and associated with cardiovascular prognosis in patients with acute coronary syndrome

Rath, Dominik; Chatterjee, Mainak; Müller, Iris; Müller, Karin; Böckmann, Corinna; Droppa, Michal; Stimpfle, Fabian; Karathanos, Athanasios; Borst, Oliver; Seizer, Peter; Langer, Harald F.; Schwab, Matthias; Gawaz, Meinrad; Geisler, Tobias

doi:10.1016/j.atherosclerosis.2014.10.021

Cited by 21 publications

(15 citation statements)

References 31 publications

(33 reference statements)

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“…Typically, miRNAs influence gene expression by inducing post-transcriptional inhibition, mRNA degradation or translation suppression ( 12 , 13 ). It has been reported that TGFβ has key roles in inflammatory responses and apoptosis ( 24 – 26 ), and is closely associated with the pathogenesis of AS ( 27 , 28 ). The present study demonstrated that miR-126 directly binds to TGFβ mRNA and inhibits its expression.…”

Section: Discussionmentioning

confidence: 99%

“…Transforming growth factor β (TGFβ) is a cytokine that has key roles in numerous biological processes, including inflammatory responses and apoptosis ( 24 – 26 ). Studies have indicated that TGFβ is closely associated with endothelial cells and the pathogenesis of AS ( 27 – 31 ). The effect of miR-126 on high-fat diet-induced endothelial permeability and apoptosis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-126 inhibits endothelial permeability and apoptosis in apolipoprotein E-knockout mice fed a high-fat diet

Cheng¹,

Wan²,

Zhou³

et al. 2017

Molecular Medicine Reports

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Endothelial dysfunction and apoptosis have key roles in the initiation and progression of atherosclerosis (AS). AS has been demonstrated to be associated with a high-fat diet, which may increase endothelial permeability and apoptosis; however, the exact mechanisms underlying the development of AS remain poorly understood. MicroRNAs (miRNAs) are vital for the regulation of cardiovascular disease, and dysregulated miRNAs have been implicated in AS. The present study investigated whether miRNA (miR)-126 regulates high-fat diet-induced endothelial permeability and apoptosis by targeting transforming growth factor β (TGFβ), a secreted protein that controls cellular proliferation and apoptosis. In the present study, apolipoprotein E (apoE)−/− mice were fed a high-fat diet in order to establish a model of AS. Mice were subcutaneously injected with a miR-126 mimic, a miR-126 antagomir or control miRNA. Reverse transcription-quantitative polymerase chain reaction was used to assess miR-126 expression, and a fluorometric assay was used to evaluate caspase-3 activity. The effects of miR-126 on the endothelial permeability of the aortic intima were also explored. Western blotting and immunohistochemical analysis were used to investigate the effects of miR-126 on B-cell lymphoma-2 (Bcl-2) and transforming growth factor (TGF) β protein expression levels. Furthermore, a luciferase assay was performed to verify whether TGFβ may be a direct target gene of miR-126. In apolipoprotein E-knockout mice, a high-fat diet reduced miR-126 expression and induced apoptosis as determined by the upregulation of caspase-3 activity. A miR-126 antagomir increased endothelial permeability and apoptosis in mice fed a high-fat diet. By contrast, an miR-126 mimic attenuated endothelial permeability and apoptosis. The reduction in miR-126 was associated with a reduction in protein expression levels of Bcl-2 and an increase of TGFβ in mice fed a high-fat diet. In addition, the present study demonstrated that miR-126 reduced TGFβ expression following binding to the 3′-untranslated region of TGFβ mRNA. The current study demonstrated a role for miR-126 in AS and identified TGFβ as a direct target of miR-126. Furthermore, the present study demonstrated that miR-126 contributed to endothelial permeability and apoptosis, and suggested that the downregulation of TGFβ may be involved in the molecular mechanisms underlying the actions of miR-126. miR-126 may therefore have potential as a novel therapeutic target for the treatment of AS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNA-126 inhibits endothelial permeability and apoptosis in apolipoprotein E-knockout mice fed a high-fat diet

Cheng¹,

Wan²,

Zhou³

et al. 2017

Molecular Medicine Reports

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show abstract

“…Only one study has previously examined TGF-β during AMI and its prognostic significance [40] . That study showed neither a difference in circulating TGF-β 1 concentrations between ACS patients and patients with stable coronary artery disease nor an association with recurrent MI and mortality.…”

Section: Discussionmentioning

confidence: 99%

Are Inflammatory Cytokines Associated with Pain during Acute Myocardial Infarction?

Imholz

Meister-Langraf

Princip

et al. 2017

Neuroimmunomodulation

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Objective: Pain and inflammation during acute myocardial infarction (AMI) have been associated with the development of posttraumatic stress disorder and may also impact negatively on somatic outcome. We investigated the relationship between pain during AMI and levels of circulating proinflammatory (tumor necrosis factor [TNF]-α, interleukin [IL]-6) and anti-inflammatory (IL-33 and tissue growth factor [TGF]-β₁) cytokines. Methods: Data were collected as part of the Myocardial Infarction - Stress Prevention Intervention (MI-SPRINT) study. We included 140 patients (mean age 59.6 years, 82.1% male) with high acute psychological distress within 48 h after MI. Fasting blood samples were drawn thereafter to measure cytokine levels. Sociodemographic factors, psychological and medical data, as well as cardiometabolic markers were assessed with questionnaires and patient interviews. Results: Linear regression models showed a significant positive correlation of pain with TGF-β₁ (b = 770.91, p = 0.031) and a significant inverse correlation of pain with IL-33 (b = -0.11, p = 0.015) after controlling for age, gender, body mass index, lifetime depression, acute stress disorder symptoms, and the prognostic Global Registry of Acute Coronary Events (GRACE) score. Pain was not associated with IL-6 but with the GRACE score (b = 0.01, p = 0.003). Pain showed no significant association with TNF-α. Conclusion: Pain during MI was associated with anti- but not proinflammatory cytokines. As IL-33 has been shown to be cardioprotective, lower IL-33 levels with more intense pain may suggest a pathway through which increased pain during MI may have an impact on the medical prognosis.

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“…Transforming growth factor- β (TGF- β ), a multifunctional inflammatory cytokine, is produced by many inflammatory cells including leucocytes, macrophages, smooth muscle cells, and platelets [ 15 – 18 ]. There are three isoforms of TGF- β : TGF- β 1, TGF- β 2, and TGF- β 3.…”

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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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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Platelet expression of transforming growth factor beta 1 is enhanced and associated with cardiovascular prognosis in patients with acute coronary syndrome

Cited by 21 publications

References 31 publications

MicroRNA-126 inhibits endothelial permeability and apoptosis in apolipoprotein E-knockout mice fed a high-fat diet

MicroRNA-126 inhibits endothelial permeability and apoptosis in apolipoprotein E-knockout mice fed a high-fat diet

Are Inflammatory Cytokines Associated with Pain during Acute Myocardial Infarction?

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

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