Cultured MFS-VSMC depicted marked phenotype changes vs. wild-type (WT) VSMC, with overexpressed cell proliferation markers but either lower (calponin-1) or higher (SM alpha-actin and SM22) differentiation marker expression.
The tumour grade and metastasis of MFS are independently associated with disease-specific survival, whereas negative surgical margins, local recurrence and blood levels of C-reactive protein and haemoglobin were not significant prognostic factors.
Compared with control-VPCs, MFS-VPCs exhibited cellular senescence as demonstrated by increased cell size, higher SA-β-gal activity and elevated levels of p53 and p21.
Apalutamid, ein neuer Androgenrezeptorinhibitor (ARI), verlängerte in der SPARTAN-Studie beim Hochrisiko-M0CRPC im Vergleich zu Placebo das metastasenfreie Überleben (MFS) signifikant.
The association of an enhanced activity by MMP-13 with an increased amount of active MMP-9 might be an important biomarker for the diagnosis of Marfan syndrome.
A significant increase in iNOS, TRPV1, VCAM (p≤0.05), NO₃⁻/NO₂⁻ ratio (p=0.002) and a significant decrease in eNOS (p=0.04) and HDL in plasma (p=0.02) in the MS vs. the C group were found.
Here we identify the molecular targets of redox stress in aortic aneurysms from MFS patients, and investigate the role of NOX4, whose expression is strongly induced by TGF-β, in aneurysm formation and progression in a murine model of MFS.
NEW & NOTEWORTHY We present the most comprehensive quantitative analysis of the ascending aortic aneurysm proteome in Marfan syndrome to date resulting in novel and potentially wide-reaching findings that expression and signaling by β<sub>3</sub>-integrin constitute a modulator of transforming growth factor-β-induced rapamycin-independent component of mammalian target of rapamycin (Rictor) signaling and physiology in aortic vascular smooth muscle cells.
In vivo noninvasive biomechanical analyses with CST offer a new, non-invasive method to identify pathologic corneal deformation responses in adults with MFS.
Here, we defined the aortic proteoglycanome using mass spectrometry, and based on the findings, investigated the large aggregating proteoglycans aggrecan and versican in human ascending TAAD and a mouse model of severe Marfan syndrome.
The MET/CEP7 ratio was about 0.65 on average, suggesting that chromosome 7 polysomy, rather than Met gene amplification, leading to the overexpression of MET protein in MFS.
Available evidence suggests that the renin-angiotensin-aldosterone (RAA) system is a good target for medical intervention on aortic root dilatation in Marfan syndrome (MFS).
Our data suggest that increased protective endothelial function, rather than ATR1 inhibition or blood pressure lowering, might be of therapeutic significance in preventing aortic root disease in MFS.
APPROACH AND RESULTS: <i>Cdh5-Cre</i> and <i>Sm22-Cre</i> transgenic mice were used to inactivate the At1ar-coding gene (<i>Agt1ar</i>) in either intimal or medial cells of both wild type and Marfan syndrome mice, respectively.
Having shown that MFS causes endothelial dysfunction and that losartan can activate endothelial function in mice and patients, we found that nitric oxide synthase (NOS) inhibition renders losartan therapeutically inactive, whereas multiple transgenic and pharmacologic models of endothelial NOS activation block aortic root dilation by correcting extracellular signal-regulated kinase signaling.
Our data suggest that increased protective endothelial function, rather than ATR1 inhibition or blood pressure lowering, might be of therapeutic significance in preventing aortic root disease in MFS.