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The Impact of a High-Salt Diet on Macrophage Development and Function in the Gut and the Liver of Mice
No full textThe prevalence of unhealthy diets poses a significant global challenge to public health and development. Among dietary risks, excessive salt intake remains a major concern. High-salt diets (HSD) have been linked to numerous health issues, including elevated blood pressure, cardiovascular diseases, and gastric cancer. Importantly, macrophages, the key immune-regulating phagocytes, have emerged as central mediators of HSD-associated adverse effects. The gut-liver axis, being the primary interface for nutritional and microbial content, is particularly vulnerable to HSD-induced stress, promoting tissue damage and persistent inflammatory responses. However, the role of macrophages in mediating these adaptations remains elusive. In this study, we investigated how short- and long-term HSD affects gut and liver macrophages in mice. Long-term HSD induced sex-dependent structural and functional changes across the gut-liver axis, including ileal pathology, gut microbial imbalance, and hepatic lipid accumulation. Functional assays showed increased intestinal permeability, indicating epithelial barrier damage, and impaired recovery in a colitis model, potentially mediated by altered macrophage phagocytic Fcγ receptors (FcγRs). Single-nucleus RNA sequencing of the ileum revealed transcriptional changes in volume regulation pathways, notably the Wnk1-dependent chloride-sensing pathway. Further 3D imaging showed increased macrophage cell volume in both tissues following long-term HSD, potentially affecting their function. High-dimensional flow cytometry enabled detailed characterization of gut and liver macrophage subsets, highlighting an increase in MHCII+Cx3cr1+CD13⁻ macrophages in the ileum of male mice and a reduction in Kupffer cells, the liver-resident macrophages, in females. A novel fate-mapping model to track fetal- and bone marrow-derived macrophages uncovered an enhanced monocyte-driven replacement of fetal-derived macrophages in both tissues with niche-specific dynamics. Functional and transcriptomic analyses further revealed dysregulated macrophage phagocytic activity in both organs, associated with FcγRIIb expression. In conclusion, these findings demonstrate that long-term HSD systemically alters macrophage function and development in the gut and liver, contributing to tissue damage and inflammatory-like responses linked to HSD. This underscores the important role of macrophages and the mechanisms they mediate in HSD-associated diseases
Synthesis and Characterization of New Amphiphilic And Chiral Squaraines
Get PDFSquaraines are a class of dye molecules obtained through reaction of mostly electron-rich molecules with squaric acid. It is an intriguing class of molecules, which has a wide field of applications and seemingly endless possibilities for future endeavors, especially in the field of optoelectronics. With its tunable properties and the many synthetic routes developed, certain characteristics with regards to the employment in photodiodes were deemed especially desirable. As previous works have beautifully shown the introduction of chirality on to the squaraine framework, which is often described as a quadrupolar D-A-D type rigid-rod –like geometry, is highly fascinating. It was discovered that the inherent central chiral information of the chirality source introduced to the framework was translated to the supramolecular level upon aggregation of the dye, resulting in measurable macroscopic circular dichroism both in colloidal solution and in thin films.
In the presented thesis the synthetic route to a new highly versatile class of squaraine was successfully developed. This class is a hybrid combining chiral information introduced by the naturally occurring amino acid alanine with additional alkyl-chains, which were found to be beneficial for the aggregation behavior of squaraines, but could not be introduced to the previous chiral squaraine class due to the nature of the chirality source. The developed synthetic route allows for various substitution patterns for this new family of chiral squaraines. As a result, it also lays the ground stone for further investigation towards other naturally occurring amino acid based squaraines. These newly obtained compounds were characterized and investigated regarding their (chiro-)optical properties in solution.
Beyond the classical field of application, optoelectronics, another ambitious combination was successfully achieved. Here the goal was the synthesis of a squaraine-based stimuli-responsive designer surfactant that could be used for micellar catalysis. It envisioned the combination of the squaric acid core with different solubilizing groups to tune the final solubility of the then amphiphilic squaraine-based surfactant.
In the presented thesis a new amphiphilic squaraine-based surfactant was synthesized, which not only combined the desired squaric acid core with a pH-indicative functional group as originally desired. Additionally, the assembly of micelles and the disassembly thereof were reliably visualized by a color change. Most importantly a new so far unique feature of the newly synthesized squaraine based surfactant results in an attractive advantage during the post-reaction purification process for the new designer surfactant compared to conventional surfactants for micellar catalysis
From Climate to Development Intelligence : Building Africa's Data Governance Systems for Resilience and Economic Growth
Get PDFThe adoption of the UN carbon-crediting mechanism at COP29 in Baku in 2024, and the growing emphasis on adaptation tracking leading up to COP30 in Belem, have marked a new phase in global climate governance. For African countries, the credibility of climate action—and access to finance—will increasingly depend on governments' capacities to generate, govern, and use reliable data.
This policy paper argues that Africa stands at a turning point: from fragmented digital systems toward an integrated data-intelligence and governance architecture that links geospatial and AI (GeoAI) analytics, harmonized measurement, reporting, and verification (MRV) systems, and transparent institutional frameworks. Drawing on insights from the Untapped Potential Index (UPI) on AI and geospatial readiness in African agri-food systems, the outcomes of the COP29 negotiations on Article 6, and the regional experience of ECOWAS in harmonizing climate-data systems, the paper outlines how Africa can consolidate its data foundations for both climate and development.
Developing such architecture serves three strategic goals: (i) strengthen Africa's credibility and participation in the global climate finance architecture through a reliable GHG tracking system; (ii) establish robust, evidence-based adaptation and resilience measurement; and (iii) build a foundation for multi-sectoral "development intelligence", linking climate, agriculture, energy, water, health, and trade
Simultaneous selection and displacement of buildings and roads for map generalization via mixed-integer quadratic programming
Get PDFResearch on map generalization has led to many algorithms for multiple elementary processes, such as object selection, aggregation, simplification, and displacement. Algorithms for different processes are usually combined to workflows or orchestrated using multi-agent systems. Here, we present a novel approach integrating object selection and displacement at an algorithmic level. We model both processes together as an optimization problem in the form of a mixed-integer quadratic program and demonstrate that it can be optimally solved using a mathematical problem solver. Moreover, we present an efficient heuristic. In experiments with roads and buildings from OpenStreetMap, our methods showed a good capability to unselect a small set of buildings whose inclusion in the output map would have caused large displacements or proximity conflicts. For a quantitative evaluation, we solved a benchmark instance once with our new model integrating selection and displacement and once with a variant of our model where the selection of objects was prescribed based on a solution found with an existing approach via simulated annealing. Comparing the two models, our integrated model yielded a solution of 33% less total cost. We conclude the article with a discussion of possible follow-up work
Hydrogen Millimeter Recombination Lines as a Tracer of Extragalactic Star Formation Rates
No full textWhen studying the structure and evolution of distant galaxies, the total star formation rate (SFR) of a given galaxy is an important observable. It is related to the gas, dust, and stellar mass content of a galaxy, and is strongly related to the ultraviolet (UV) radiation field, which affects the physical and chemical state of the star-forming interstellar gas. The SFR can be inferred from several observational tracers, such as UV emission (from massive stars), far-infrared (FIR) emission (from dust heated by massive stars), radio synchrotron emission (from relativistic electrons accelerated in supernovae), or hydrogen recombination line emission (in ionized gas around massive stars, the so-called HII regions). All have their advantages and disadvantages. A promising SFR tracer that has not yet been extensively studied for distant galaxies is the millimeter-wavelength hydrogen recombination line (mm-RL) emission. In this work, I investigate how the physical conditions in HII regions affect the amplification and attenuation of mm-RL emission. We harvest the Atacama Large Millimeter-submillimeter Array (ALMA) data archive and use our own IRAM 30m telescope observations to assemble mm-RL detections towards nearby (within a few hundred Mpc) star-forming galaxies. Our ALMA archive sample consists of the 20 brightest infrared star-forming galaxies, while the IRAM 30m observations target six nearby star-forming galaxies with prior cm-wavelength RL detections. We detect mm RL emission from 9 galaxies in the ALMA sample, while no lines are detected in the IRAM 30m sample. We compare the implied SFR of these galaxies when derived from the mm-RL emission and from their FIR emission, and find a linear correlation that is consistent with measurements of individual massive star-forming regions in our Milky Way galaxy, stretching over eight orders of magnitude. We find that several sources show mm-RL emission suffering from maser amplification, and that maser amplification cannot be ruled out even for galactic sources. We evaluate the quality of mm-RL emission as a reliable SFR tracer and suggest that mm-RL emission, in combination with FIR emission, can be used to trace the recent star formation history
Tenure arrangement, cadastral survey system, and land valuation : addressing tenure insecurity in the aquatic land settlements of Riau Islands Province, Indonesia
Get PDFRiau Islands Province of Indonesia poses a land administration challenge due to its marine setting and culturally rooted coastline settlements. The settlements rapid growth, intricate administration, unclear rights and their spatial realization, and the absence of appropriate valuation frameworks has compounded tenure insecurity in coastal areas. The insecurity leads to overlapping claims and disputes, as well as undermines effective taxation and investment. Academics have underscored the importance of crafting context-specific solutions by considering the important role of people, governance, and technology. Strengthening tenure security in coastal areas is not only a national priority under Indonesia's Agrarian Reform program but also aligns with international agendas such as the Sustainable Development Goals (SDGs), the Fit-for-Purpose Land Administration approach, and FAO's Voluntary Guidelines on Responsible Tenure Governance. The aim of this thesis is to develop and assess the tailored solutions to obtain legal, spatial, and value-based certainty for strengthening tenure security of aquatic lands in coastline settlements.
First, a specially designed tenure arrangement was developed to define optimal tenure forms that are compliant with legal frameworks, community needs, spatial plans, and the unique physical characteristics. Using Analytic Hierarchy Process (AHP) and Fuzzy Technique for Order Preference by Similarity to Ideal Solution (Fuzzy TOPSIS), the study identified five otimal tenure forms: hak pakai (Right of Use), hak guna bangunan (Right to Build), Surat Keterangan Tanah (Possession Letter), Hak komunal (Communal Right) and Numpang Bangun (NB system). These forms reflect a hybrid tenure system that acknowledges both statutory and customary rights. The framework also accounts for spatial constraints and physical conditions to guide more sensitive tenure allocation, including the identification of rights, restrictions, and responsibilities. This finding suggests the recognition of hybrid tenure for the system in securing tenure and reflecting the diverse ways tenure forms are managed in practice. Second, in addressing spatial certainty, the thesis assessed the application of Unmanned Aerial Vehicle (UAV) for cadastral boundary mapping. Two semi-automatic methods—Object-Based Image Analysis (OBIA) and Mapflow.AI (Mask R-CNN)—were used to delineate building footprints as one of the proxies for parcel boundaries. OBIA consistently demonstrated higher accuracy in completeness, correctness, and quality. We found that both methods struggled in areas with dense, irregularly shaped buildings; and performed better in more distinct and water-locked building clusters where buildings are clearly separated by roads or bodies of water. By evaluating these methods' applicability to different areas and building types, the study offers guidance on implementing image-based techniques for spatially securing tenure. These findings support the viability of UAV-based methods as cost-effective and purposively accurate tools for spatially defining tenure. Third, the study developed a context-specific, GIS parcel-based hedonic mass land valuation. Economic, legal, and physical-environmental attributes were identified through literature and field observations, with the latter factor shown to be the most relevant value factors in coastline settlements. A comparison-score method was used to calculate land value, followed by multiple regression analysis to validate model robustness. Although there may be some unexplained variability remaining, the results exhibit a strong explanatory capacity and offer reliable land value information.
This thesis concludes that the strategies developed through hybrid-tenure arrangements, UAV-based semi-automatic cadastral boundary generation systems, and adaptive valuation models offer promising and complementary solutions. They demonstrate the potential multidimensional security services to address tenure insecurity in the aquatic land settlements of the Riau Islands Province
Residence of mice in metabolic cages reduces experimental kidney inflammation through stress-induced glucocorticoids
Get PDFStickstoffreduzierte Nährstoffversorgung bei heranwachsenden Schweinen : Ein Beitrag zur Ressourcenschonung und Verbesserung der Robustheit
Get PDFFür eine nachhaltige und umweltschonende Schweineproduktion ist die Reduktion der Stickstoff (N) und Phosphor (P) Ausscheidung von zentraler Bedeutung. Dieses Ziel kann nur durch interdisziplinäre Forschungsansätze von Tierzucht (Verbesserung der N/P-Futtereffizienz) und Tierernährung (Optimierung der N/P-Verfügbarkeit) erreicht werden. Aus züchterischer Sicht ist die Frage bislang weitestgehend ungeklärt, welchen Einfluss genetischen Faktoren und mögliche Genotyp × Umwelt-Interaktionen (GUI, hier: Genotyp × Fütterungsgruppe) auf die N/P-Ausscheidung bzw. Nährstoffeffizienz haben. Daher war das Ziel des Projektes, die Bedeutung von genetischen Effekten und GUI auf Merkmale der Futtereffizienz bei Mastschweinen beim Einsatz von N/P-reduzierten Rationen zu erfassen. Darüber hinaus sollten die Auswirkungen der N/P-Reduktion auf Tiergesund-heit, Mikrobiom und Tierverhalten beurteilt werden.
Im vorliegenden Projekt wurden bei 103 Kreuzungsschweinen (Piétrain × Deutsche Landrasse) auf dem Campus Frankenforst unter möglichst praxisnahen Bedingungen leistungsgeprüft. Die Tiere stammten von 20 KB-Ebern ab, welche das genetische Potential der Rasse Piétrain abbildeten. Die Tiere wurden in zwei Fütterungsgruppen „Kontrolle (C)“ und „Versuchsgruppe (LP)“ mit stark bzw. sehr stark reduzierter N/P-Gehalt, gemäß DLG-Fütterungsrichtlinien, eingeteilt. Gemäß den Ergebnissen der am ITW durchgeführten Nährstoffanalysen, lagen die Rohprotein- und Phosphorkonzentrati-onen der gelieferten Futtermittel in den erlaubten Toleranzbereichen. Allerdings konnte die geplante N/P-Absenkung der LP-Gruppe nicht in allen vier durchgeführten Durchgängen und Mastphasen realisiert werden. Von jedem Versuchstier lagen Informationen über Merkmale der Mast- und Fleischleistung, Fettsäuremuster, Futteraufnahme, N- und P-Ausscheidung im Kot sowie über die, mittels Blutharnstoffge-halt geschätzte N-Ausscheidung im Harn vor.
Die Fütterungsgruppe hatte einen signifikanten Effekt auf die N/P-Aufnahme, Verdaulichkeit und Ausscheidung. Für diese Merkmale wurden innerhalb der Mastab-schnitte in der Regel niedrige bis mittlere h2 (0,00-0,39) und für die N-Ausscheidung über den Harn hohe h2 (0,57-0,77) geschätzt werden. Über die gesamte Mast lagen sowohl die h2 der N/P-assoziierten Merkmale als auch die geschätzten GUI-Varianzverhältnisse auf einem eher niedrigen Niveau (h2 bzw. gi2 2-Werte sind teilweise innerhalb der Mastphase zu beobachten. Dies gilt insbesondere für die N/P-Verdaulichkeiten (alle Mastphasen) und Ausscheidungen über den Kot (P: Mittelmast, N: Endmast) mit gi2-Werten >0,15. Diese Ergebnisse können als Indikator für relevanten GUI interpretiert werden.
Unerwünschte Auswirkungen der N/P-Reduktion auf die Tiergesundheit und die Veränderungen des Tierverhaltens sowie auf die Zusammensetzung der Knochen konnten im Projekt nicht festgestellt werden. Auch konnten keine signifikanten Beziehungen zwischen P-Ausscheidung im Kot und P-Gehalt im Knochen beobachtet werden.
Der Einfluss der N/P-reduzierten Fütterung auf das Darm-Mikrobiom wurde im zweiten Teil des Projektes untersucht. Die Charakterisierung der mikrobiellen Gemeinschaft basierte auf aufbereiteten 16S rRNA Sequenz Daten. Insgesamt wurden 208 Proben von vier Darmabschnitten (Jejunum, Ileum, Caecum und Colon) von 52 Tieren sequenziert. Es zeigten sich klare Unterschiede zwischen Dünn- und Dickdarmabschnitte in der Besiedlung der verschiedenen Stämme und Familien der Mikroben (Alpha-Diversität). Es konnten ebenfalls deutliche Einflüsse auf die Variabilität zwischen den Proben (Beta-Diversität) durch die Faktoren Durchgang, Fütterungsgruppe innerhalb des Durchgangs und das Geschlecht beobachtet werden. Der Einfluss des Mikrobioms auf relevante Merkmale wurde durch die Mikrobiability (m2) geschätzt. Dabei zeigte sich, dass die Schätzwerte der h2 (genetischer Einfluss) im Vergleich zu den m2-Werten (Mikrobiom-Einfluss), mit Ausnahme für das Merkmal der täglichen Zunahme mit der m2 im Colon, auf einem deutlich höheren Niveau lagen. Das Mikrobiom des Dünndarms (Jejunum und Ileum) schien mit Ausnahme der N/P-Verdaulichkeit im Jejunum keinen Einfluss auf die Variation der Merkmale zu haben, während in den Dickdarmabschnitten hohe m2-Werte nur für zwei Futtereffizienzmerkmale geschätzt wurden.
Im Rahmen der mikrobiomweiten Assoziationsstudien (MWAS) wurde der Einfluss einzelner bakterieller Spezies auf die Mastleistungs-, Futtereffizienz- und N/P-assoziierte Merkmale untersucht. Dabei wurden sowohl in Dünn- als auch in Dickdarmproben jeweils 13 nominal oder tendenziell nominal signifikante darmspezifische Amplikon-Sequenziervarianten (ASVs) für die Merkmale P-Ausscheidung über den Kot, N-Ausscheidung über den Harn und tägliche Zunahme gefunden.
Zusammenfassend zeigen die Ergebnisse der vorliegenden Mikrobiom-Studie, dass die Zusammensetzung des Mikrobioms mit hoher Wahrscheinlichkeit die untersuchten Mast- und Effizienzmerkmale beeinflusst. Neben der additiv-genetischen Varianz könnte die Mikrobiom Variabilität auch vor dem Hintergrund potentieller GUI züchterisch genutzt werden. Darüber hinaus könnte das Mikrobiom als Biomarker für schwer zu erfassende Merkmale wie z. B. die N/P-Nährstoffeffizienz dienen. Auf Grund des geringen Stichprobenumfangs sind jedoch weitere Untersuchungen erforderlich, um die genannten Ergebnisse zu validieren.For a sustainable and environmentally friendly pig production, a reduction of nitrogen (N) and phosphorus (P) excretion is of crucial importance. This target can be achieved by interdisciplinary approaches involving animal genetics (improvement of the N/P-efficiency) and animal nutrition (optimising the dietary N/P-availability). From the perspective of animal breeding, there is a lack of knowledge concerning influence of the genetic factors and possible genotype×environmental-interactions (GUI) on N/P-excretion. There for, the aim of the project was to determine the impact of genetic factors and GUI on feed efficiency of fattening pigs fed with N/P-reduced diets. In addition, possible consequences of a N/P-reduced feeding regime on animal health, behaviour and microbiota were evaluated.
In the present study, 103 Pietrain (Pi)×Landrace (LR) growing-finishing pigs were performance tested under farm conditions on the Campus Frankenforst of the University of Bonn. The animals were originated from 20 artificial insemination boars (AI-boar) intended to reflect the genetic performance potential of Pi. The pigs were divided into the two groups “control (C)” and “low N/P (LP)” and were fed with “strong N/P-reduced” and “very strong N/P-reduced” diets, respectively, according to the DLG-recommendations.
Following the results of the analysis of the diets, the raw protein and P content were within the range of tolerance of the legal declaration. However, the extend of N/P restriction varied due to practical conditions and could not be consistently realised in every batch of the diet.Data of fattening and slaughter performance, meat quality, feed N/P excretion of feces as well as the urinary N excretion based on the blood urea N were available for every investigated animal.
The N/P intake, digestibility and calculated excretion were significantly influenced by the dietary N/P content. These traits showed a low to moderate heritability (h2) (0.00-0.39), except for estimated urinary N excretion exhibiting the highest values (0.57-0.77). Estimated AI boar×group effects (gi2), indicating a GUI, were generally below h2-values. When h2 and gi2 exceeded 0.1, additional evidence for GUI was provided by correlation coefficients of predicted progeny differences between feeding groups (0.3-0.8).
Undesirable effects on animal health, behaviour, and bone composition as well as bone density due to the N/P-reduction were not observed within this study. In addition, no relevant relationships among P-excretion of feces and P-content in bone samples were detected.
In the second part of the project, the impact of a N/P-reduction on the microbiome was investigated. The characterization of the microbial community based on processed 16S rRNA sequences. In total, 208 samples of four gut sections (jejunum, ileum, caecum, and colon) obtained from 52 selected pigs were sequenced.
Significant differences for microbial families and genera were observed between small (jejunum, ileum) and large intestine (caecum, colon) in terms of alpha diversity. Furthermore, a distinct impact of the factors run, group within run and gender on the variability (beta-diversity) among the samples was observed. The impact of the microbiome on relevant traits was estimated by the microbiability (m2). In general, the estimates for h2 (genetic impact) were higher compared to the estimated of m2 (impact of the microbiome), except for average daily gain in the colon. The microbiome of the small intestine (jejunum and ileum) did not influence the expression of the traits, except for the N/P-digestibility through the jejunum. In contrast, in the colon high m2 were estimated for two feed efficiency traits.
Based on a microbiome-wide association study (MWAS), the significance of single microbial species on fattening performance, feed-efficiency and N/P-associated traits was investigated. In total, 13 nominal or putative nominal significant intestine specific amplicon-sequence variants (ASVs) for small-intestine and colon samples were detected, affecting P-exception in feces, urinary N-excretion, and average daily gain.
In conclusion, the results of this study revealed, that the composition of the microbiome affects all here investigated fattening performance and feed efficiency traits to a large extend. Beside additive-genetic variance, the variance of the microbiome can be implemented into the breeding process. This might be particularly beneficial against the background of the existence of GUI. Furthermore, important information of microbiome might be useful as biomarkers for traits like N/P-efficiency traits, that are difficult to record under practical conditions. However, because of the limited number of records it is necessary to validate the obtained results, using an enlarged data set
Multi-Person Pose Tracking in Videos
Get PDFThis thesis addresses the complex challenges of multi-person pose estimation and tracking in dynamic, real-world environments. Motivated by advancements in artificial intelligence and the growing need for natural human-machine interaction, this research focuses on developing robust computer vision systems that can accurately estimate and track human poses. These systems have broad applications, ranging from healthcare and surveillance to autonomous driving, sports analysis, and entertainment. However, real-world scenarios, especially those involving multiple interacting individuals, frequently result in keypoint inaccuracies due to occlusions and overlapping body parts, as seen in sports where highly articulated poses are common. Effective pose tracking requires robust occlusion handling and the ability to preserve identities, even across videos.
Previous approaches formulated multi-person pose tracking as spatiotemporal graph partitioning problems, which are computationally expensive and unsuitable for real-time applications. More recent methods using flow-, motion-, or appearance-based assignments struggle when individuals are occluded, and appearance-based methods face challenges with partial occlusions and visually similar individuals. Additionally, existing datasets for multi-person pose tracking are sparsely annotated and lack identity information.
This research tackles several key challenges, including occlusions, motion blur, crowded scenes, and varying lighting conditions, which heavily impact pose estimation and tracking accuracy. We propose a top-down multi-person pose estimation and tracking framework, with the core contribution being a self-supervised keypoint correspondence network that recovers missed detections, associates keypoints across video frames, and restores broken tracks due to occlusions. Moreover, recognizing the limitations of existing datasets, we introduce PoseTrack21 - a densely annotated dataset designed to improve training and evaluation in multi-person pose tracking, multi-object tracking, and person search. PoseTrack21 includes comprehensive annotations for keypoints, bounding boxes, and person identities, enabling joint evaluation across these tasks. Additionally, we present a Gated Attention Transformer model that integrates appearance and keypoint-based similarities through a novel gating mechanism, improving the robustness of pose tracking systems. This model includes a matching layer to eliminate redundant detections and a pose-conditioned re-identification network to handle occlusions, enhancing tracking consistency.
Our proposed methods are extensively evaluated on the PoseTrack 2017, 2018, and PoseTrack21 datasets, demonstrating their effectiveness. The contributions of this thesis establish a foundation for more efficient multi-person pose tracking systems, advancing the state-of-the-art in this crucial area of computer vision
Tragen Fibrosierung und Hypoxie im Herzgewebe zum kardioprotektiven Effekt in Cx3cr1-defizienten Mäusen nach transverser aortaler Konstriktion bei?
Get PDFDie linksventrikuläre Hypertrophie als Resultat der chronisch erhöhten linksventrikulären Druckbelastung ist ein häufiges Krankheitsbild mit einer hohen Übergangsrate in eine Herzinsuffizienz. Vor diesem Hintergrund gewinnt die in vorherigen Studien beschriebene Kardioprotektion bei Cx3cr1-defizienten Mäusen an Bedeutung. Cx3cr1 ist ein Chemokinrezeptor, der vor allem auf Makrophagen exprimiert wird und eine regulatorische Funktion besitzt. Um die Mechanismen der Kardioprotektion im Cx3cr1-knock-out Modell zu untersuchen, wurden in dieser Arbeit die Hypoxie der Kardiomyozyten sowie die Fibrosierung anhand von Kollagen I und III im murinen Modell einer durch transaortale Konstriktion (TAC) erhöhten linksventrikulären Druckbelastung analysiert.
Die Hypoxie im Herzgewebe nach TAC wurde anhand der Transkriptionsfaktoren der akuten Hypoxie (HIF-1a) und der chronischen Hypoxie (HIF-2a) analysiert. Die Ergebnisse zeigen keine signifikanten Unterschiede, allerdings zeigte sich tendenziell eine unterschiedliche Regulation zwischen den Mauslinien bei HIF-2a, welches die Makrophagen-Motilität und dadurch die Fibrosierung beeinflusst.
Die weiteren Untersuchungen dieser Arbeit deuten darauf hin, dass die beobachtete Kardioprotektion auf die reduzierte Kollagen-I-Ablagerung bei Cx3cr1-Defizienz im Vergleich zum Wildtyp zurückzuführen ist. Eine erhöhte Kollagen-I-Ablagerung ist mit einer erhöhten Steifheit und einer reduzierten diastolischen Funktion des Herzens assoziiert, während Kollagen III eine flexiblere Narbenbildung fördert. Die Kollagen-III-Akkumulation im Herzgewebe war bei den Cx3cr1-defizienten Mäusen signifikant erhöht.
Die Inhibition von Cx3cr1 stellt somit ein vielversprechendes zukünftiges Therapieziel bei der Behandlung der linksventrikulären Hypertrophie und der häufig daraus resultierenden Herzinsuffizienz dar