Abstract
Marfan syndrome (MS) is of the most common connective tissue disorders. Although most patients have mutations in the fibrillin-1 gene (FBN1) and more than 1,700 mutations have been described, there are no mutations in less than 10% of patients. Aortic dilation is the most important complication; it involves chronic inflammatory processes and endothelial dysfunction. Prospective study from March 2015 to January 2017, in a cohort of 32 patients of MS confirmed by Ghent criteria and 35 controls of both genders, with a median age of 26 years (18–56). Patients had no comorbidities such as diabetes, hypertension, and/or neoplasms. They were not being treated with statin, NSAIDs, calcium antagonists, oral nitrates, and/or beta-blockers during 7 days prior to the study and patients with smoking history in the last 4 years. Controls were matched by age and gender. We analyzed endothelial dysfunction by flow-mediated vasodilation in the brachial artery, determining the maximum peak flow in the reactive hyperemia phase with a Philips Envisor device with Doppler capability. Its correlation with serum levels of biological markers that could participate in endothelial dysfunction pathways such as ratio, , citrulline, TNFα, IL-1, IL-6, IL-10, IL-8, osteopontin, ICAM, VCAM, and was determined. Endothelial dysfunction was found in 21 MS patients (65%). The aortic annulus (AAo) was of 27 mm (22–40) and 24 mm (22–30) (p = 0.04) in MS patients with and without dysfunction. The level of ratio, was of 108.95 ± 12.05 nM/ml in controls vs. 170.04 ± 18.76 nM/ml in MS (p = 0.002), was of 33.78 ± 3.41 vs. 43.95 ± 2.59 nM/ml (p = 0.03), citrulline 62.65 ± 3.46 vs. 72.81 ± 4.35 μMol/ml (p = 0.06). VCAM median was 39 pg/ml (0–86) vs. 32 pg/ml (11–66) (p = 0.03), respectively. The correlation of VCAM with triglycerides (TG) was of 0.62 (p = 0.005). There were no differences in TNFα, IL-1, IL-6, IL-8, IL-10, and osteopontin. MS endothelial dysfunction is related to aortic diameters, and increased levels of VCAM, L-citrulline and ratio, . VCAM-1 has a significant correlation with TG and could play a significant role in endothelial dysfunction.
Highlights
Marfan syndrome (MS) is rare disease with a dominant autosomal hereditary pattern that has an overall incidence of 3/10,000
A total of 32 MS patients were considered of which 21 (66%) presented familiar background of MS and 20 (63%) suffered from crystalline luxation. 10 males and 13 females showed aortic dilation with a mean dilation value of 46 ± 11 mm, whereas the non-dilated individuals showed an average value of 30 ± 2 mm
In MS, there is flow-mediated endothelial dysfunction, which is correlated with an increase of the aortic diameter, NO−3 /NO−2 ratio, NO−2 and lipids
Summary
Marfan syndrome (MS) is rare disease with a dominant autosomal hereditary pattern that has an overall incidence of 3/10,000. It is related to 1,700 mutations in the fibrillin-1 (FBN1) gene (Dietz, 2017). The FBN1 gene is 250 kb long; it is composed of 65 exons, and is located in chromosome 15q-21.1. FBN1 is essential component of elastic and inelastic connective tissues. FBN1 helps in the transference of the hemodynamic burden and in the alignment of the fibers along the direction of parietal stress. FBN1 is involved in the protective mechanisms that prevent over-distension of elastin, improving arterial elasticity. This can result in flow-mediated vasodilation (Eberth et al, 2009). The augmented activity of the TGFB signaling pathway may lead to elastic fiber disruption and to an increase in collagen reservoirs in MS (Yang H.H. et al, 2010)
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