A combined proteomic and transcriptomic approach shows diverging molecular mechanisms in thoracic aortic aneurysm development in patients with tricuspid- and bicuspid aortic valve.

Thoracic aortic aneurysm is a pathological local dilatation of the aorta, potentially leading to aortic rupture or dissection. The disease is a common complication of patients with bicuspid aortic valve, a congenital disorder present in 1-2% of the population. Using two dimensional fluorescence difference gel electrophoresis proteomics followed by mRNA expression, and alternative splicing analysis of the identified proteins, differences in dilated and nondilated aorta tissues between 44 patients with bicuspid and tricuspid valves was examined. The pattern of protein expression was successfully validated with LC-MS/MS. A multivariate analysis of protein expression data revealed diverging protein expression fingerprints in patients with tricuspid compared with the patients with bicuspid aortic valves. From 302 protein spots included in the analysis, 69 and 38 spots were differentially expressed between dilated and nondilated aorta specifically in patients with tricuspid and bicuspid aortic valve, respectively. 92 protein spots were differentially expressed between dilated and nondilated aorta in both phenotypes. Similarly, mRNA expression together with alternative splicing analysis of the identified proteins also showed diverging fingerprints in the two patient groups. Differential splicing was abundant but the expression levels of differentially spliced mRNA transcripts were low compared with the wild type transcript and there was no correlation between splicing and the number of spots. Therefore, the different spots are likely to represent post-translational modifications. The identification of differentially expressed proteins suggests that dilatation in patients with a tricuspid aortic valve involves inflammatory processes whereas aortic aneurysm in patients with BAV may be the consequence of impaired repair capacity. The results imply that aortic aneurysm formation in patients with bicuspid and tricuspid aortic valves involve different biological pathways leading to the same phenotype.

Photovoltaic nanowires affect human lung cell proliferation under illumination conditions.

Using light to interact with cells is a promising way to steer cell behavior with minimal perturbation. Besides optogenetics, photovoltaic nanostructures such as nanowires can be used to interact with cells using light as a switch. Photovoltaic nanowires have, for instance, been used to stimulate neurons. However, the effects of the photovoltaic activity on cells are still poorly understood and characterized. Here, we investigate the effects of the photovoltaic activity of p-i-n nanowire arrays on A549 human lung adenocarcinoma cells. We have cultured A549 cells on top of vertical arrays of indium phosphide p-i-n nanowires (photovoltaic nanowires), with and without illumination to assess the effects of the nanowire photovoltaic activity on cells. We show that there is a higher proportion of dormant cells when the p-i-n nanowire arrays are illuminated. However, there is no difference in the proportion of dormant cells when the p-i-n nanowires are coated with oxide, which suggests that carrier injection in the cell medium (in this case, the release of electrons from the tip of the nanowires) is an important factor for modulating cell proliferation on photovoltaic nanowires. The results open up for interesting applications of photovoltaic nanowires in biomedicine, such as using them as a dormancy switch.

Matrix metalloproteinase 14 and 19 expression is associated with thoracic aortic aneurysms.

OBJECTIVE: It is hypothesized that an altered turnover of extracellular matrix mediated by matrix metalloproteinases (MMPs) is present in thoracic aortic aneurysms. Here, we analyzed the occurrence of MMPs and MMP inhibitors in ascending aortic aneurysms in patients with bicuspid and tricuspid aortic valves. METHODS: Expression of 23 MMPs and their inhibitors was measured in aortic intima/media and adventitia in 109 patients (40 tricuspid, 69 bicuspid, 68 with aortic diameter≥4.5 cm, and 41 with ≤4.0 cm) using Affymetrix Exon arrays (Affymetrix, Santa Clara, Calif). Gene expression was confirmed by quantitative real-time polymerase chain reaction. Principal components analysis was used to study differences in gene expression. Immunohistochemistry was used to study protein expression. RESULTS: We detected messenger RNA expression for gelatinases (MMP2 and MMP9), stromelysin 3 (MMP11), all membrane bound MMPs (MMP14, MMP15, MMP16, MMP17, MMP24, MMP25), MMP19, MMP21, and MMP28 in ascending aorta. No expression of collagenases was detected. Principal components analysis showed that changes in mRNA expression between dilated and nondilated aorta were mainly detected in patients with tricuspid aortic valves. MMP14 and MMP19 showed higher expression in dilated aortas and MMP19 expression correlated positively to maximal aortic diameter in patients with tricuspid aortic valves (Rho=0.61, P=.004, and Rho=0.57, P=.008, using raw and body surface area-corrected aortic diameter, respectively). Immunohistochemical staining demonstrated increased medial expression of MMP14 and MMP19 in dilated aorta. CONCLUSIONS: The present study identifies MMP14 and MMP19 as proteolytic enzymes potentially involved in aneurysm formation in the ascending aorta of patients with tricuspid aortic valves.

Ljungan virus detected in bank voles (Myodes glareolus) and yellow-necked mice (Apodemus flavicollis) from Northern Italy.

Identified in 1998, Ljungan virus (LV; Picornaviridae) causes type 1 diabetes-like symptoms and myocarditis in bank voles (Myodes glareolus) from Sweden and Denmark, and may be a zoonotic agent of several important diseases (e.g., intrauterine fetal death, type 1 diabetes, Guillain-Barré syndrome, and myocarditis). Using a real-time reverse transcriptase-polymerase chain reaction assay and sequence analysis, we detected LV in bank voles, and for the first time, in yellow-necked mice (Apodemus flavicollis) collected during 2006 from a site in northern Italy. The global distribution of LV and its role as a mammalian pathogen deserve further attention.