The Moexipril HCl discrete “on-top-of disturbed TGF-b signaling” contribution of inflammation in the disease pathogenesis might be the reason that MFS was never seen as an inflammatory disease. Now it seems that TGF-b levels in blood could possibly function as a biomarker to predict the onset of an aortic phenotype. In addition, when MFS patients have been diagnosed with aortic root dilatation, increased blood M-CSF levels can indicate the aggressiveness of the aortic disease in order to differentiate MFS patients needing frequent or less frequent follow-up of aortic root diameters. With the knowledge that inflammation plays a key role in the aortic root dilatation rate, an active search can be started to find even stronger biomarkers for disease progression. When looking at a relationship between blood TGF-b levels and chest deformities, no significant correlation was found, even though genes related to TGF-b signaling are differentially regulated strongly in this MFS feature. MFS patients with other skeletal features, mitral valve prolapse, dural ectasia and pneumothorax revealed no gene expression differences when comparing them to MFS patients without these specific features. Historically, aortic disease in MFS is considered a disease of the aortic media, where we indeed find medial necrosis and inflammatory cells. However, our histological results also show significantly increased counts of CD8+ T-cells in the Marfan aortas, emphasizing a role for the aortic adventitia. In line with these data, Lindeman and co-workers found that collagen microarchitecture in the aortic adventitia of MFS patients was impaired, whereas the medial layer is relatively intact when it comes to endurance of pressure. Basically, the adventitia serves as an “external stent” determining maximal diameter of the vessel. When its structure is impaired its “stent” function is lost. The authors also showed that fibrillin-1 is more abundantly present in the adventitia of healthy control tissue, rather than in the media of the aortic wall. Therefore, it seems that FBN1 mutations could easily affect the organization of the collagen fibers in the aortic adventitia. TGF-b signaling is known to enhance collagen production, however, the quality of the collagen triple helix and the network of fibers Hexyl Chloroformate formed is presumably more important that the amount of collagen alone. Defective fibrillin-1 in MFS apparently leads to an impaired collagen fiber/network organization. Aortic damage due to impaired resistance to pressure may cause collagen damage, and collagen degradation products resulting from this process may induce inflammation.