Possible extracardiac predictors of aortic dissection in Marfan syndrome.
BACKGROUND
According to previous studies, aortic diameter alone seems to be insufficient to predict the event of aortic dissection in Marfan syndrome (MFS). Determining the optimal schedule for preventive aortic root replacement (ARR) aortic growth rate is of importance, as well as family history, however, none of them appear to be decisive. Thus, the aim of this study was to search for potential predictors of aortic dissection in MFS.


METHODS
A Marfan Biobank consisting of 79 MFS patients was established. Thirty-nine MFS patients who underwent ARR were assigned into three groups based on the indication for surgery (dissection, annuloaortic ectasia and prophylactic surgery). The prophylactic surgery group was excluded from the study. Transforming growth factor-β (TGF-β) serum levels were measured by ELISA, relative expression of c-Fos, matrix metalloproteinase 3 and 9 (MMP-3 and -9) were assessed by RT-PCR. Clinical parameters, including anthropometric variables - based on the original Ghent criteria were also analyzed.


RESULTS
Among patients with aortic dissection, TGF-β serum level was elevated (43.78 ± 6.51 vs. 31.64 ± 4.99 ng/l, p < 0.0001), MMP-3 was up-regulated (Ln2α = 1.87, p = 0.062) and striae atrophicae were more common (92% vs. 41% p = 0.027) compared to the annuloaortic ectasia group.


CONCLUSIONS
We found three easily measurable parameters (striae atrophicae, TGF-β serum level, MMP-3) that may help to predict the risk of aortic dissection in MFS. Based on these findings a new classification of MFS, that is benign or malignant is also proposed, which could be taken into consideration in determining the timing of prophylactic ARR.
Bence
B
Agg
Heart and Vascular Center, Semmelweis University, Városmajor str, 68, 1122 Budapest, Hungary. kalman.benke@gmail.com.
Kálmán
K
Benke
Bálint
B
Szilveszter
Miklós
M
Pólos
László
L
Daróczi
Balázs
B
Odler
Zsolt B
ZB
Nagy
Ferenc
F
Tarr
Béla
B
Merkely
Zoltán
Z
Szabolcs
D000328:Adult; D000784:Aortic Dissection / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D001014:Aortic Aneurysm / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D015415:Biomarkers / Q000097:blood; D019917:Blood Vessel Prosthesis Implantation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000473:pathology; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008875:Middle Aged; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D012042:Registries; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D014015:Tissue Banks; D053773:Transforming Growth Factor beta1 / Q000097:blood; D055815:Young Adult
D015415:Biomarkers; D005819:Genetic Markers; D016760:Proto-Oncogene Proteins c-fos; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9