Impact of delayed type hypersensitivity arthritis on development of heart failure by aortic constriction in mice.

AIMS: Patients with rheumatoid arthritis (RA) have increased risk of heart failure (HF). The mechanisms and cardiac prerequisites explaining this association remain unresolved. In this study, we sought to determine the potential cardiac impact of an experimental model of RA in mice subjected to HF by constriction of the ascending aorta. METHODS: Aorta was constricted via thoracotomy and placement of o-rings with inner diameter 0.55 mm or 0.66 mm, or sham operated. RA-like phenotype was instigated by delayed-type hypersensitivity arthritis (DTHA) two weeks after surgery and re-iterated after additional 18 days. Cardiac magnetic resonance imaging (MRI) was performed before surgery and at successive time points throughout the study. Six weeks after surgery the mice were euthanized, blood and tissue were collected, organ weights were documented, and expression levels of cardiac foetal genes were analysed. In a supplemental study, DTHA-mice were euthanized throughout 14 days after induction of arthritis, and blood was analysed for important markers and mediators of RA (SAP, TNF-α and IL-6). In order to put the latter findings into clinical context, the same molecules were analysed in serum from untreated RA patients and compared to healthy controls. RESULTS: Significant elevations of inflammatory markers were found in both patient- and murine blood. Furthermore, the DTHA model appeared clinically relevant when compared to the inflammatory responses observed in three prespecified RA severity disease states. Two distinct trajectories of cardiac dysfunction and HF development were found using the two o-ring sizes. These differences were consistent by both MRI, organ weights and cardiac foetal gene expression levels. Still, no difference within the HF groups, nor within the sham groups, could be found when DTHA was induced. CONCLUSION: DTHA mediated systemic inflammation did not cause, nor modify HF caused by aortic constriction. This indicates other prerequisites for RA-induced cardiac dysfunction.

House Dust Mite Exposure Causes Increased Susceptibility of Nasal Epithelial Cells to Adenovirus Infection.

Adenovirus (AdV) infections in the respiratory tract may cause asthma exacerbation and allergic predisposition, and the house dust mite (HDM) may aggravate virus-induced asthma exacerbations. However, the underlying mechanisms of whether and how AdV affects asthmatic patients remains unclear. To address this question, we investigated nasal epithelial cells (NAEPCs) derived from a pediatric exacerbation study cohort for experimental analyses. We analyzed twenty-one different green-fluorescent protein- and luciferase-tagged AdV types in submerged 2D and organotypic 3D cell culture models. Transduction experiments revealed robust transduction of AdV type 5 (AdV5) in NAEPCs, which was associated with an increased uptake of AdV5 in the presence of HDM. In healthy and asthmatic NAEPCs exposed to HDM before infection, we observed a time- and dose-dependent increase of AdV5 uptake associated with upregulation of entry receptors for AdV5. Furthermore, electron microscopic and histologic analyses of 3D cell cultures revealed an impairment of the respiratory cilia after HDM exposition. This ex vivo pilot study shows the impact of AdV infection and HDM exposition in a primary cell culture model for asthma.

Exercise-induced decline in the density of LYVE-1-positive lymphatic vessels in human skeletal muscle.

BACKGROUND: The investigation of lymphatic function and biology and its microvascular influence on tissue integrity, development and failure in various disease conditions constitutes an important field of medical research. To date several investigations were carried out investigating alterations of lymphatic vessel density under medical conditions e.g. in transplanted or failing heart. However, only few studies investigated aspects of exercise induced plasticity of lymphatic vessels. STUDY OBJECTIVE: It was investigated, if alterations in lymphatic density can be observed in human skeletal muscle as a response to endurance exercise and if potential changes might be related to the distribution of myofibres. METHODS: Muscle biopsies were taken from vastus lateralis muscle of male cyclists under resting conditions. Lymphatic capillary density and myofibre distribution were determined prior, as well as over the time course of a cycling training intervention. Lymphatic capillaries were stained by immunohistochemistry using LYVE-1 and Podoplanin antibodies. Myofibre distribution was classified by myofibrillar ATPase staining. RESULTS: The density of LYVE-1/+ capillaries in skeletal muscle was observed to decrease significantly over the time course of the exercise intervention. It was further noticed that in consecutive cross sections a small part of vessels however showed either podoplanin or LYVE-1 staining. We did not recognize correlations of LYVE-1/+ vessel density to the distribution of the myofibre spectrum in trained skeletal muscle. CONCLUSION: It was concluded that lymphatic vessels are rather normally distributed in skeletal muscle not dependent on a predominant myofibre type. The partial not observed co staining of LYVE-1 and podoplanin might be influenced by a shift in vessel phenotype. The finding of significantly decreased LYVE-1/+ capillary density over the time course of the applied exercise intervention gives rise to the assumption that exercise induced stimuli were able to induce alterations of lymphangiogenetic responses on a structural level.