Ventricular arrhythmia in 80 patients.

<p> Five patients had >1 ventricular event.</p

Baseline characteristics according to arrhythmia.

<p> ACE-I identifies angiotensin converting enzyme inhibitors; ARB, angiotensin-receptor blockers; HDL cholesterol, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol, and nsVT, non-sustained ventricular tachycardia.</p><p>–Whitney test for continuous data and the Fisher's exact test for nominal and categorical data. Mann</p><p> Three patients received two or three different classes of drugs.</p

<i>FBN1</i> mutation characteristics according to arrhythmia.

<p>–Whitney test for continuous data and the Fisher's exact test for nominal and categorical data. Mann</p

Baseline characteristics of 80 patients with Marfan syndrome and <i>FBN1</i> mutation.

<p>± standard deviation or numbers (percentage). Mean </p

ROC curve analysis identifies NT-proBNP serum levels >618 pg/ml as a threshold for increased risk of VTE.

<p>The area under the curve is .919 (95% confidence interval .850 to.988; <i>P</i><.001; upper panel). For better identification of cut-offs separating high and low risk, we separately display sensitivity and specificity (lower panel).</p

According to the revised Ghent nosology [17] we identified disease causality for 80 <i>FBN1</i> mutations, as missense mutations affecting/creating cysteine residues in 25 (30%), nonsense mutations in 15 (19%), inframe and out of frame deletion/insertions in 14 (18%), missense mutations affecting conserved residues of the EGF consensus sequence in 9 (11%), other missense mutations in 9 (11%), splice site mutations in 6 (8%), and missense mutations creating cysteine residues in a EGF consensus sequence in 2 (3%) [17].

<p>According to the revised Ghent nosology <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081281#pone.0081281-Loeys1" target="_blank">[17]</a> we identified disease causality for 80 <i>FBN1</i> mutations, as missense mutations affecting/creating cysteine residues in 25 (30%), nonsense mutations in 15 (19%), inframe and out of frame deletion/insertions in 14 (18%), missense mutations affecting conserved residues of the EGF consensus sequence in 9 (11%), other missense mutations in 9 (11%), splice site mutations in 6 (8%), and missense mutations creating cysteine residues in a EGF consensus sequence in 2 (3%) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0081281#pone.0081281-Loeys1" target="_blank">[17]</a>.</p

Kaplan–Meier curves indicate an increased cumulative risk for VTE depending on presence of nsVT (upper panel), of NT-proBNP serum levels >618 pg/ml (middle panel), and of <i>FBN1</i> gene mutation in exons 24–32 (lower panel).

<p>Kaplan–Meier curves indicate an increased cumulative risk for VTE depending on presence of nsVT (upper panel), of NT-proBNP serum levels >618 pg/ml (middle panel), and of <i>FBN1</i> gene mutation in exons 24–32 (lower panel).</p

Gremlin-1 expression on aortic tissue of LDS patients.

<p>Paraffin-embedded aortic tissue specimen of LDS patients (n = 3) were double stained with anti-Gremlin-1 (brown staining) and anti-CD34 (red staining; C) or anti-smooth muscle actin (red staining; B, D–F). Endothelial cells throughout the vessel wall showed expression for Gremlin-1 including ECs of the intima (B) and of vessels within the media (C) and the adventitia (D and in more detail in E). Gremlin-1 positive staining was also observed on smooth muscle cells of the media (B, C) as well as on vessel surrounding smooth muscle cells in the adventitial layer (D, E). In aortic tissue specimen of healthy controls (n = 3), a similar staining pattern without gross differences of staining intensity was observed as shown for a small vessel within the adventitia (F). In A, an isotype control instead of primary antibody was used revealing the specificity of the staining (EC = endothelial cell, SMC = smooth muscle cell; magnification A–D, F: 400×; E: 1000×; scale bar represents 20 µm in A–D and F and 8 µm in E).</p

Elevated Gremlin-1 protein expression in LDS-OECs.

<p>The Gremlin-1 protein expression in LDS-OECs was compared to OECs isolated from sex- and age-matched healthy donors. Immunoblotting followed by quantification revealed that the Gremlin-1 protein amount was increased in all three LDS-OEC clones compared to their respective control.</p

Members of the TGF-β superfamily with altered mRNA expression levels in LDS-OECs compared to healthy controls.

<p>* signal log ratio of LDS-OEC compared to healthy control, determined in microarray analysis; ^† expression fold change of LDS-OEC compared to healthy control, converted from microarray data; ^‡ relative gene expression in LDS-OEC compared to healthy control, determined in quantitative PCR analysis and normalized to <i>GAPDH</i> expression.</p