scholarly journals Circulating Transforming Growth Factor-β in Marfan Syndrome

Circulation ◽  
2009 ◽  
Vol 120 (6) ◽  
pp. 526-532 ◽  
Author(s):  
Peter Matt ◽  
Florian Schoenhoff ◽  
Jennifer Habashi ◽  
Tammy Holm ◽  
Christel Van Erp ◽  
...  
Keyword(s):  
Growth Factor ◽  
Marfan Syndrome ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β

scholarly journals Serological level of transforming growth factor-β as a predictive biomarker of aortic enlargement in patients with Marfan syndrome

2017 ◽  
Vol 8 (1) ◽  
pp. 61-66
Author(s):  
Andrey S Rudoy ◽  
Alexey M Uryvaev
Keyword(s):  
Risk Factors ◽  
Growth Factor ◽  
Marfan Syndrome ◽  
Aortic Root ◽  
Transforming Growth Factor ◽  
Aortic Rupture ◽  
Imaging Techniques ◽  
Elevated Serum ◽  
Transforming Growth Factor Β ◽  
Absolute Size

Marfan syndrome - an inherited, autosomal dominant disease with an expected rate of 3-5/10 000 or fraction of 20-25% of new mutations, accompanied by violation of the connective tissue that occurs as a result of gene mutations FBN1, coding for the synthesis of fibrillin-1, performing the most important role in the modulation physiological bioavailability TGF-β (transforming growth factor-β). Prediction of aortic rupture is based on the identification of risk factors: family history, the absolute size of the aortic root, the rate of expansion of the aorta, which are based on the results of the history and techniques of imaging ultrasound, CT, MRI. At the same time there is a chance of developing aortic rupture under normal aortic root size and the absence of any risk factors, as well as after the prophylactic prosthetic aortic root. This makes it necessary to search for alternative prognostic markers, threatening bundle and rupture of the aorta. Article verified the predictive role of TGF-β as a serological biomarker for assessing the extension of the aortic root in patients with Marfan syndrome (n = 23, F : M / 7 : 16; 33 ± 9.3 years). The article describes the patterns between TGF-β and the size and the reconstruction of the aneurysm of the thoracic aorta. It was found that elevated levels of serum TGF-β1 (49.1 ng/ml Vs 29.15 ng/ml in the control, p < 0.05) in patients with MS diagnosed with an extension of the aortic root (Z > 1.96) can serve as a serological marker to poor prognosis, accompanied by an increase in the size of the aortic root. In patients with normal-sized aorta, and after aortic reconstruction serum TGFβ1 not elevated. Serum TGFβ may be a promising target for therapeutic, diagnostic and prognostic tactics which are not based on imaging techniques.

Circulating transforming growth factor-β as a prognostic biomarker in Marfan syndrome

2013 ◽  
Vol 168 (3) ◽  
pp. 2441-2446 ◽  
Author(s):  
Romy Franken ◽  
Alexander W. den Hartog ◽  
Vivian de Waard ◽  
Leo Engele ◽  
Teodora Radonic ◽  
...  
Keyword(s):  
Growth Factor ◽  
Marfan Syndrome ◽  
Transforming Growth Factor ◽  
Prognostic Biomarker ◽  
Transforming Growth Factor Β

scholarly journals Inhibition of transforming growth factor-β signaling in myeloid cells ameliorates aortic aneurysmal formation in Marfan syndrome

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0239908
Author(s):  
Hironori Hara ◽  
Sonoko Maemura ◽  
Takayuki Fujiwara ◽  
Norifumi Takeda ◽  
Satoshi Ishii ◽  
...  
Keyword(s):  
Growth Factor ◽  
Marfan Syndrome ◽  
Transforming Growth Factor ◽  
Receptor Gene ◽  
Myeloid Cells ◽  
Inflammatory Cells ◽  
Transforming Growth Factor Β ◽  
Elastic Fibers ◽  
Raw264.7 Macrophages

Increased transforming growth factor-β (TGF-β) signaling contributes to the pathophysiology of aortic aneurysm in Marfan syndrome (MFS). Recent reports indicate that a small but significant number of inflammatory cells are infiltrated into the aortic media and adventitia in MFS. However, little is known about the contribution of myeloid cells to aortic aneurysmal formation. In this study, we ablated the TGF-β type II receptor gene Tgfbr2 in myeloid cells of Fbn1C1039G/+ MFS mice (Fbn1C1039G/+;LysM-Cre/+;Tgfbr2fl/fl mice, hereinafter called Fbn1C1039G/+;Tgfbr2MyeKO) and evaluated macrophage infiltration and TGF-β signaling in the aorta. Aneurysmal formation with fragmentation and disarray of medial elastic fibers observed in MFS mice was significantly ameliorated in Fbn1C1039G/+;Tgfbr2MyeKO mice. In the aorta of Fbn1C1039G/+;Tgfbr2MyeKO mice, both canonical and noncanonical TGF-β signals were attenuated and the number of infiltrated F4/80-positive macrophages was significantly reduced. In vitro, TGF-β enhanced the migration capacity of RAW264.7 macrophages. These findings suggest that TGF-β signaling in myeloid cells promotes aortic aneurysmal formation and its inhibition might be a novel therapeutic target in MFS.

scholarly journals Anti-TGFβ (Transforming Growth Factor β) Therapy With Betaglycan-Derived P144 Peptide Gene Delivery Prevents the Formation of Aortic Aneurysm in a Mouse Model of Marfan Syndrome

2021 ◽  
Author(s):  
Cristina Arce ◽  
Isaac Rodríguez-Rovira ◽  
Karo De Rycke ◽  
Karina Durán ◽  
Victoria Campuzano ◽  
...  
Keyword(s):  
Growth Factor ◽  
Aortic Aneurysm ◽  
Mouse Model ◽  
Marfan Syndrome ◽  
Palliative Treatment ◽  
Transforming Growth Factor ◽  
Preventive Treatment ◽  
Transforming Growth Factor Β ◽  
Mrna Levels ◽  
Tgfβ Signaling

Objective: We investigated the effect of a potent TGFβ (transforming growth factor β) inhibitor peptide (P144) from the betaglycan/TGFβ receptor III on aortic aneurysm development in a Marfan syndrome mouse model. Approach and Results: We used a chimeric gene encoding the P144 peptide linked to apolipoprotein A-I via a flexible linker expressed by a hepatotropic adeno-associated vector. Two experimental approaches were performed: (1) a preventive treatment where the vector was injected before the onset of the aortic aneurysm (aged 4 weeks) and followed-up for 4 and 20 weeks and (2) a palliative treatment where the vector was injected once the aneurysm was formed (8 weeks old) and followed-up for 16 weeks. We evaluated the aortic root diameter by echocardiography, the aortic wall architecture and TGFβ signaling downstream effector expression of pSMAD2 and pERK1/2 by immunohistomorphometry, and Tgfβ1 and Tgfβ2 mRNA expression levels by real-time polymerase chain reaction. Marfan syndrome mice subjected to the preventive approach showed no aortic dilation in contrast to untreated Marfan syndrome mice, which at the same end point age already presented the aneurysm. In contrast, the palliative treatment with P144 did not halt aneurysm progression. In all cases, P144 improved elastic fiber morphology and normalized pERK1/2-mediated TGFβ signaling. Unlike the palliative treatment, the preventive treatment reduced Tgfβ1 and Tgfβ2 mRNA levels. Conclusions: P144 prevents the onset of aortic aneurysm but not its progression. Results indicate the importance of reducing the excess of active TGFβ signaling during the early stages of aortic disease progression.

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