Author + information
- Toru Suzuki, MD⁎ (, )
- Santi Trimarchi, MD,
- Daigo Sawaki, MD,
- Viviana Grassi, MD,
- Elena Costa, MD,
- Vincenzo Rampoldi, MD,
- Ryozo Nagai, MD and
- Kim Eagle, MD
- ↵⁎Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
To the Editor:
Circulating transforming growth factor (TGF)-beta has received recent attention because it may potentially serve as a biomarker for therapeutic monitoring of aortic remodeling processes in patients with Marfan syndrome (1,2). TGF-beta and its actions are regulated by the elastic protein fibrillin-1. TGF-beta is bound in a complexed form to fibrillin-1, which, on pathogenic insult, is disrupted to release and activate the TGF-beta molecule, which in turn acts on vascular cells to induce aortic remodeling. Mutation of fibrillin-1 leading to aberrant regulation of TGF-beta is thought to be a central pathogenic mechanism of Marfan syndrome (3). Recent discoveries that renin-angiotensin system inhibitors directly act on dysregulation of TGF-beta to affect aortic remodeling have opened up new therapeutic possibilities for this disease (1,4).
Whether TGF-beta is increased in aortic conditions in the non-Marfan adult, however, has remained unknown. Here, we show that circulating TGF-beta levels are elevated in patients with acute aortic dissection. Efforts have been made to develop diagnostic biomarkers of this disease because aortic dissection is a catastrophic aortic disease with high mortality and morbidity that requires immediate diagnosis and treatment. Aortic dissection and rupture are also primary cardiovascular manifestations in patients with Marfan syndrome who reach adolescence.
In 28 non-Marfan patients with acute aortic dissection defined as being within 24 h of symptom onset, TGF-beta levels as measured by a commercially available assay (TGF-beta 1 Quantikine immunoassay, R&D Systems, Minneapolis, Minnesota) showed elevations at 24.5 ± 12.9 ng/ml (median 25.4 ng/ml) that are approximately 5-fold elevations compared with normal controls (5.4 ± 2.8 ng/ml) (5). When categorized according to dissection type, Stanford type A dissections showed approximately 2-fold elevations (p < 0.01, nonparametric Mann-Whitney U test) in type A patients (28.5 ± 14.7 ng/ml [n = 20]; median 28.7 ng/ml) compared with type B dissections (14.4 ± 6.1 ng/ml [n = 8]; median 14.6 ng/ml). Circulating TGF-beta levels were therefore markedly elevated in patients with type A dissections, which are often associated with a worse prognosis and require immediate medical attention. Collectively, our findings, although preliminary, suggest that circulating TGF-beta levels may also serve as a potential biomarker of aortic disease in the non-Marfan adult.
Further questions that remain to be addressed are whether circulating TGF-beta levels can be used to monitor remodeling dynamics in aortic conditions such as aortic dissection and aneurysms in the non-Marfan adult and whether they will be responsive to pharmacological treatment. For example, whether circulating TGF-beta levels will serve as a reliable surrogate biomarker to assess aortic expansion in type B dissections that might predict the need for surgery and response to medication during the course of treatment will need to be addressed. More sensitive assays may be necessary to allow accurate assessment as necessary for therapeutic monitoring in the chronic phase of disease progression. Nonetheless, we believe that circulating TGF-beta is a promising biomarker for potential use in diagnostic and therapeutic assessment of aortic diseases.
Please note: Drs. Suzuki, Trimarchi, and Sawaki contributed equally to this work.
- American College of Cardiology Foundation