@article{GoetzRueckschlossBalketal.2023,
  author    = {G{\"o}tz, Lisa and Rueckschloss, Uwe and Balk, G{\"o}zde and Pfeiffer, Verena and Erg{\"u}n, S{\"u}leyman and Kleefeldt, Florian},
  title     = {The role of carcinoembryonic antigen-related cell adhesion molecule 1 in cancer},
  series = {Frontiers in Immunology},
  volume    = {14},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2023.1295232},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357250},
  year      = {2023},
  abstract  = {The Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin superfamily. CEACAM1 was shown to be a prognostic marker in patients suffering from cancer. In this review, we summarize pre-clinical and clinical evidence linking CEACAM1 to tumorigenicity and cancer progression. Furthermore, we discuss potential CEACAM1-based mechanisms that may affect cancer biology.},
  language  = {en}
}
@article{GruschwitzHartungKleefeldtetal.2023,
  author    = {Gruschwitz, Philipp and Hartung, Viktor and Kleefeldt, Florian and Erg{\"u}n, S{\"u}leyman and Lichthardt, Sven and Huflage, Henner and Hendel, Robin and Kunz, Andreas Steven and Pannenbecker, Pauline and Kuhl, Philipp Josef and Augustin, Anne Marie and Bley, Thorsten Alexander and Petritsch, Bernhard and Grunz, Jan-Peter},
  title     = {Standardized assessment of vascular reconstruction kernels in photon-counting CT angiographies of the leg using a continuous extracorporeal perfusion model},
  series = {Scientific Reports},
  volume    = {13},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-023-39063-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357912},
  year      = {2023},
  abstract  = {This study evaluated the influence of different vascular reconstruction kernels on the image quality of CT angiographies of the lower extremity runoff using a 1st-generation photon-counting-detector CT (PCD-CT) compared with dose-matched examinations on a 3rd-generation energy-integrating-detector CT (EID-CT). Inducing continuous extracorporeal perfusion in a human cadaveric model, we performed CT angiographies of eight upper leg arterial runoffs with radiation dose-equivalent 120 kVp acquisition protocols (CTDIvol 5 mGy). Reconstructions were executed with different vascular kernels, matching the individual modulation transfer functions between scanners. Signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were computed to assess objective image quality. Six radiologists evaluated image quality subjectively using a forced-choice pairwise comparison tool. Interrater agreement was determined by calculating Kendall's concordance coefficient (W). The intraluminal attenuation of PCD-CT images was significantly higher than of EID-CT (414.7 ± 27.3 HU vs. 329.3 ± 24.5 HU; p < 0.001). Using comparable kernels, image noise with PCD-CT was significantly lower than with EID-CT (p ≤ 0.044). Correspondingly, SNR and CNR were approximately twofold higher for PCD-CT (p < 0.001). Increasing the spatial frequency for PCD-CT reconstructions by one level resulted in similar metrics compared to EID-CT (CNRfat; EID-CT Bv49: 21.7 ± 3.7 versus PCD-CT Bv60: 21.4 ± 3.5). Overall image quality of PCD-CTA achieved ratings superior to EID-CTA irrespective of the used reconstruction kernels (best: PCD-CT Bv60; worst: EID-CT Bv40; p < 0.001). Interrater agreement was good (W = 0.78). Concluding, PCD-CT offers superior intraluminal attenuation, SNR, and CNR compared to EID-CT in angiographies of the upper leg arterial runoff. Combined with improved subjective image quality, PCD-CT facilitates the use of sharper convolution kernels and ultimately bears the potential of improved vascular structure assessability.},
  language  = {en}
}
@article{MadrahimovMutsenkoNatanovetal.2023,
  author    = {Madrahimov, Nodir and Mutsenko, Vitalii and Natanov, Ruslan and Radaković, Dejan and Klapproth, Andr{\´e} and Hassan, Mohamed and Rosenfeldt, Mathias and Kleefeldt, Florian and Aleksic, Ivan and Erg{\"u}n, S{\"u}leyman and Otto, Christoph and Leyh, Rainer G. and Bening, Constanze},
  title     = {Multiorgan recovery in a cadaver body using mild hypothermic ECMO treatment in a murine model},
  series = {Intensive Care Medicine Experimental},
  volume    = {11},
  journal   = {Intensive Care Medicine Experimental},
  doi       = {10.1186/s40635-023-00534-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357381},
  year      = {2023},
  abstract  = {Background Transplant candidates on the waiting list are increasingly challenged by the lack of organs. Most of the organs can only be kept viable within very limited timeframes (e.g., mere 4-6 h for heart and lungs exposed to refrigeration temperatures ex vivo). Donation after circulatory death (DCD) using extracorporeal membrane oxygenation (ECMO) can significantly enlarge the donor pool, organ yield per donor, and shelf life. Nevertheless, clinical attempts to recover organs for transplantation after uncontrolled DCD are extremely complex and hardly reproducible. Therefore, as a preliminary strategy to fulfill this task, experimental protocols using feasible animal models are highly warranted. The primary aim of the study was to develop a model of ECMO-based cadaver organ recovery in mice. Our model mimics uncontrolled organ donation after an "out-of-hospital" sudden unexpected death with subsequent "in-hospital" cadaver management post-mortem. The secondary aim was to assess blood gas parameters, cardiac activity as well as overall organ state. The study protocol included post-mortem heparin-streptokinase administration 10 min after confirmed death induced by cervical dislocation under full anesthesia. After cannulation, veno-arterial ECMO (V-A ECMO) was started 1 h after death and continued for 2 h under mild hypothermic conditions followed by organ harvest. Pressure- and flow-controlled oxygenated blood-based reperfusion of a cadaver body was accompanied by blood gas analysis (BGA), electrocardiography, and histological evaluation of ischemia-reperfusion injury. For the first time, we designed and implemented, a not yet reported, miniaturized murine hemodialysis circuit for the treatment of severe hyperkalemia and metabolic acidosis post-mortem. Results BGA parameters confirmed profound ischemia typical for cadavers and incompatible with normal physiology, including extremely low blood pH, profound negative base excess, and enormously high levels of lactate. Two hours after ECMO implantation, blood pH values of a cadaver body restored from < 6.5 to 7.3 ± 0.05, pCO2 was lowered from > 130 to 41.7 ± 10.5 mmHg, sO2, base excess, and HCO3 were all elevated from below detection thresholds to 99.5 ± 0.6\%, - 4 ± 6.2 and 22.0 ± 6.0 mmol/L, respectively (Student T test, p < 0.05). A substantial decrease in hyperlactatemia (from > 20 to 10.5 ± 1.7 mmol/L) and hyperkalemia (from > 9 to 6.9 ± 1.0 mmol/L) was observed when hemodialysis was implemented. On balance, the first signs of regained heart activity appeared on average 10 min after ECMO initiation without cardioplegia or any inotropic and vasopressor support. This was followed by restoration of myocardial contractility with a heart rate of up to 200 beats per minute (bpm) as detected by an electrocardiogram (ECG). Histological examinations revealed no evidence of heart injury 3 h post-mortem, whereas shock-specific morphological changes relevant to acute death and consequent cardiac/circulatory arrest were observed in the lungs, liver, and kidney of both control and ECMO-treated cadaver mice. Conclusions Thus, our model represents a promising approach to facilitate studying perspectives of cadaveric multiorgan recovery for transplantation. Moreover, it opens new possibilities for cadaver organ treatment to extend and potentiate donation and, hence, contribute to solving the organ shortage dilemma.},
  language  = {en}
}
@phdthesis{Kleefeldt2020,
  author    = {Kleefeldt, Florian},
  title     = {Einfluss von CEACAM1 auf die endotheliale Funktion},
  doi       = {10.25972/OPUS-20172},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201726},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Dem Endothel, welches die luminale Oberfl{\"a}che aller Blutgef{\"a}ße auskleidet, kommt eine wichtige Barrierefunktion zwischen Blut und Gewebe zu. Nur durch eine bedarfsgerechte Justierung dieser Barriere, die den Durchtritt von Molek{\"u}len und Zellen reguliert, kann die Gewebehom{\"o}ostase aufrechterhalten werden. Dabei ist das Endothel nicht nur passive Barriere, sondern auch an dieser dynamischen Regulation aktiv beteiligt. St{\"o}rungen oder Fehlregulationen dieser Prozesse f{\"u}hren zu Pathologien, z.B. Arteriosklerose. Es ist seit l{\"a}ngerem bekannt, dass Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1), ein Mitglied der Immunglobulin-Superfamilie, die Bildung und Morphogenese neuer Blutgef{\"a}ße beeinflusst. Die spontane Entwicklung kleiner Arteriosklerose-{\"a}hnlicher L{\"a}sionen in CEACAM1 knockout (Cc1-/-) M{\"a}usen zeigt, dass CEACAM1 auch f{\"u}r die Hom{\"o}ostase ausgereifter Blutgef{\"a}ße von Bedeutung ist. Ziel dieser Dissertationsarbeit war daher, den Einfluss von CEACAM1 auf wesentliche Aspekte der Endothelfunktion in Aorten in situ bzw. in Endothelzellkulturen in vitro zu analysieren. Es konnte zun{\"a}chst gezeigt werden, dass CEACAM1-defiziente Endothelzellen im Vergleich zu Wildtyp (WT) Endothelzellen eine rundlichere Zellmorphologie mit meanderf{\"o}rmigen Zellgrenzen und interzellul{\"a}ren L{\"u}cken aufweisen. Diese morphologischen Unterschiede stimmen mit Befunden in situ an Aorten von WT und Cc1-/- M{\"a}usen {\"u}berein. Weiterhin wurde eine Translokation der endothelialen NO-Synthase (eNOS) von der Zellmembran in den peri-nukle{\"a}ren Bereich bei CEACAM1-Defizienz festgestellt. Die erhobenen Daten bieten zwei m{\"o}gliche Erkl{\"a}rungen daf{\"u}r. Einerseits k{\"o}nnte CEACAM1 durch Interaktion mit eNOS als Membrananker fungieren. Daneben wiesen CEACAM1-defiziente Endothelzellen eine erh{\"o}hte Expression des Enzyms APT1 auf, welches eNOS depalmitoyliert. Die daraus resultierende, ebenfalls nachgewiesene geringere Palmitoylierung k{\"o}nnte auch zur verminderten Membran-lokalisation von eNOS beitragen. Zur endothelialen Funktion geh{\"o}rt, die Adh{\"a}sion von Blutzellen an die Gef{\"a}ßwand weitestgehend zu beschr{\"a}nken. CEACAM1-defiziente Endothelzellen zeigten im Vergleich zu WT Endothelzellen eine verst{\"a}rkte Adh{\"a}sivit{\"a}t gegen{\"u}ber murinen und humanen Monozyten. {\"A}hnliche Unterschiede wurden f{\"u}r Aortenexplantate aus WT und Cc1-/- M{\"a}usen festgestellt. Dies ist einerseits mit einer verst{\"a}rkten Expression des Zelladh{\"a}sionsmolek{\"u}ls ICAM-1 bei CEACAM1-Defizienz erkl{\"a}rbar. Dar{\"u}ber hinaus vermittelt die Glykokalyx anti-adh{\"a}sive Eigenschaften. Aus Vorbefunden war bekannt, dass die endotheliale Glykokalyx in der Aorta von Cc1-/- M{\"a}use reduziert ist. Im Rahmen dieser Arbeit konnte dies auf eine verst{\"a}rkte Expression der Glykokalyx-degradierenden Enzyme MMP9, Chondroitinase sowie Hyaluronidase-2 in Cc1-/- Endothelzellen zur{\"u}ckgef{\"u}hrt werden. Eine erh{\"o}hte Permeabilit{\"a}t stellt einen Indikator f{\"u}r ein dysfunktionales Endothel, eines der initialen Schritte in der Pathogenese der Arteriosklerose, dar. Zur Analyse der aortalen Permeabilit{\"a}t wurde ein modifizierter Miles-Assay etabliert. Unter Verwendung etablierter muriner Arteriosklerosemodelle konnte gezeigt werden, dass dieser Assay eine St{\"o}rung der vaskul{\"a}ren Permeabilit{\"a}t bereits vor Auftreten makroskopischer Ver{\"a}nderungen zuverl{\"a}ssig detektiert. Im Rahmen der folgenden Analysen an WT und Cc1-/- M{\"a}usen zeigte sich ein altersabh{\"a}ngiger Effekt von CEACAM1 auf die Gef{\"a}ßpermeabilit{\"a}t: Aorten von 3 Monate alten Cc1-/- M{\"a}use wiesen eine im Vergleich zum WT erh{\"o}hte Gef{\"a}ßpermeabilit{\"a}t auf, welche wahrscheinlich Folge einer verz{\"o}gerten Gef{\"a}ßreifung ist. Im Alter von 9 Monaten zeigte sich dagegen ein entgegengesetztes Bild. Dies wurde auf eine verst{\"a}rkte Expression des die Barriere sch{\"a}digenden Inflammationsmediators TNF-α in 9 Monate alten WT M{\"a}usen zur{\"u}ckgef{\"u}hrt. Außerdem modulierte CEACAM1 die TNF-α-vermittelte Lockerung der endothelialen Barriere, indem es die Phosphorylierung von Adherens Junction Proteinen beeinflusste. Basal stabilisierte CEACAM1 die endotheliale Barriere durch Hemmung der Phosphorylierung von Caveolin-1, welches Adherens Junctions destabilisiert. Unter Einfluss von TNF-α war CEACAM1 verst{\"a}rkt im Bereich von Adherens Junctions lokalisiert und rekrutierte dort Src-Kinase. Src-Kinase wiederum destabilisierte Adherens Junctions durch Phosphorylierung von β-Catenin, was in verst{\"a}rkter Gef{\"a}ßpermeabilit{\"a}t resultierte. Dagegen f{\"u}hrte TNF-α in CEACAM1-defizienten Endothelzellen zu einer Dephosphorylierung von Caveolin-1 und β-Catenin, wodurch Adherens Junctions und damit die endotheliale Barriere stabilisiert wurden. Diese CEACAM1-abh{\"a}ngige differenzielle Regulation der Stabilit{\"a}t von Adherens Junctions unter TNF-α tr{\"a}gt wahrscheinlich maßgeblich zu den Unterschieden der vaskul{\"a}ren Permeabilit{\"a}t in 3 bzw. 9 Monate alten WT und Cc1-/- M{\"a}usen bei. Zusammenfassend konnte im Rahmen dieser Arbeit nachgewiesen werden, dass CEACAM1 zentrale Funktionen des Endothels und hier{\"u}ber die Hom{\"o}ostase reifer Gef{\"a}ße beeinflusst. Da eine Expression von CEACAM1 auch in arteriosklerotischen Plaques nachgewiesen werden konnte, soll in weiteren Untersuchungen auch der Beitrag von CEACAM1 zur arteriosklerotischen Plaquebildung analysiert werden.},
  subject      = {Endothel},
  language  = {de}
}
@article{UpcinHenkeKleefeldtetal.2021,
  author    = {Upcin, Berin and Henke, Erik and Kleefeldt, Florian and Hoffmann, Helene and Rosenwald, Andreas and Irmak-Sav, Ster and Aktas, Huseyin Bertal and R{\"u}ckschloß, Uwe and Erg{\"u}n, S{\"u}leyman},
  title     = {Contribution of adventitia-derived stem and progenitor cells to new vessel formation in tumors},
  series = {Cells},
  volume    = {10},
  journal   = {Cells},
  number    = {7},
  doi       = {10.3390/cells10071719},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242577},
  year      = {2021},
  abstract  = {Blocking tumor vascularization has not yet come to fruition to the extent it was hoped for, as angiogenesis inhibitors have shown only partial success in the clinic. We hypothesized that under- appreciated vascular wall-resident stem and progenitor cells (VW-SPCs) might be involved in tumor vascularization and influence effectiveness of anti-angiogenic therapy. Indeed, in patient samples, we observed that vascular adventitia-resident CD34\(^+\) VW-SPCs are recruited to tumors in situ from co-opted vessels. To elucidate this in detail, we established an ex vivo model using concomitant embedding of multi-cellular tumor spheroids (MCTS) and mouse aortic rings (ARs) into collagen gels, similar to the so-called aortic ring assay (ARA). Moreover, ARA was modified by removing the ARs' adventitia that harbors VW-SPCs. Thus, this model enabled distinguishing the contribution of VW-SPCs from that of mature endothelial cells (ECs) to new vessel formation. Our results show that the formation of capillary-like sprouts is considerably delayed, and their number and network formation were significantly reduced by removing the adventitia. Substituting iPSC-derived neural spheroids for MCTS resulted in distinct sprouting patterns that were also strongly influenced by the presence or absence of VW-SPCs, also underlying the involvement of these cells in non-pathological vascularization. Our data suggest that more comprehensive approaches are needed in order to block all of the mechanisms contributing to tumor vascularization.},
  language  = {en}
}
@article{GruschwitzHartungKleefeldtetal.2023,
  author    = {Gruschwitz, Philipp and Hartung, Viktor and Kleefeldt, Florian and Peter, Dominik and Lichthardt, Sven and Huflage, Henner and Grunz, Jan-Peter and Augustin, Anne Marie and Erg{\"u}n, S{\"u}leyman and Bley, Thorsten Alexander and Petritsch, Bernhard},
  title     = {Continuous extracorporeal femoral perfusion model for intravascular ultrasound, computed tomography and digital subtraction angiography},
  series = {PLoS One},
  volume    = {18},
  journal   = {PLoS One},
  number    = {5},
  issn      = {1932-6203},
  doi       = {10.1371/journal.pone.0285810},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350136},
  year      = {2023},
  abstract  = {Objectives We developed a novel human cadaveric perfusion model with continuous extracorporeal femoral perfusion suitable for performing intra-individual comparison studies, training of interventional procedures and preclinical testing of endovascular devices. Objective of this study was to introduce the techniques and evaluate the feasibility for realistic computed tomography angiography (CTA), digital subtraction angiography (DSA) including vascular interventions, and intravascular ultrasound (IVUS). Methods The establishment of the extracorporeal perfusion was attempted using one formalin-fixed and five fresh-frozen human cadavers. In all specimens, the common femoral and popliteal arteries were prepared, introducer sheaths inserted, and perfusion established by a peristaltic pump. Subsequently, we performed CTA and bilateral DSA in five cadavers and IVUS on both legs of four donors. Examination time without unintentional interruption was measured both with and without non-contrast planning CT. Percutaneous transluminal angioplasty and stenting was performed by two interventional radiologists on nine extremities (five donors) using a broad spectrum of different intravascular devices. Results The perfusion of the upper leg arteries was successfully established in all fresh-frozen but not in the formalin-fixed cadaver. The experimental setup generated a stable circulation in each procedure (ten upper legs) for a period of more than six hours. Images acquired with CT, DSA and IVUS offered a realistic impression and enabled the sufficient visualization of all examined vessel segments. Arterial cannulating, percutaneous transluminal angioplasty as well as stent deployment were feasible in a way that is comparable to a vascular intervention in vivo. The perfusion model allowed for introduction and testing of previously not used devices. Conclusions The continuous femoral perfusion model can be established with moderate effort, works stable, and is utilizable for medical imaging of the peripheral arterial system using CTA, DSA and IVUS. Therefore, it appears suitable for research studies, developing skills in interventional procedures and testing of new or unfamiliar vascular devices.},
  language  = {en}
}
@article{KarnatiSeimetzKleefeldtetal.2021,
  author    = {Karnati, Srikanth and Seimetz, Michael and Kleefeldt, Florian and Sonawane, Avinash and Madhusudhan, Thati and Bachhuka, Akash and Kosanovic, Djuro and Weissmann, Norbert and Kr{\"u}ger, Karsten and Erg{\"u}n, S{\"u}leyman},
  title     = {Chronic Obstructive Pulmonary Disease and the Cardiovascular System: Vascular Repair and Regeneration as a Therapeutic Target},
  series = {Frontiers in Cardiovascular Medicine},
  volume    = {8},
  journal   = {Frontiers in Cardiovascular Medicine},
  issn      = {2297-055X},
  doi       = {10.3389/fcvm.2021.649512},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235631},
  year      = {2021},
  abstract  = {Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide and encompasses chronic bronchitis and emphysema. It has been shown that vascular wall remodeling and pulmonary hypertension (PH) can occur not only in patients with COPD but also in smokers with normal lung function, suggesting a causal role for vascular alterations in the development of emphysema. Mechanistically, abnormalities in the vasculature, such as inflammation, endothelial dysfunction, imbalances in cellular apoptosis/proliferation, and increased oxidative/nitrosative stress promote development of PH, cor pulmonale, and most probably pulmonary emphysema. Hypoxemia in the pulmonary chamber modulates the activation of key transcription factors and signaling cascades, which propagates inflammation and infiltration of neutrophils, resulting in vascular remodeling. Endothelial progenitor cells have angiogenesis capabilities, resulting in transdifferentiation of the smooth muscle cells via aberrant activation of several cytokines, growth factors, and chemokines. The vascular endothelium influences the balance between vaso-constriction and -dilation in the heart. Targeting key players affecting the vasculature might help in the development of new treatment strategies for both PH and COPD. The present review aims to summarize current knowledge about vascular alterations and production of reactive oxygen species in COPD. The present review emphasizes on the importance of the vasculature for the usually parenchyma-focused view of the pathobiology of COPD.},
  language  = {en}
}
@article{KleefeldtUpcinBoemmeletal.2022,
  author    = {Kleefeldt, Florian and Upcin, Berin and B{\"o}mmel, Heike and Schulz, Christian and Eckner, Georg and Allmanritter, Jan and Bauer, Jochen and Braunger, Barbara and Rueckschloss, Uwe and Erg{\"u}n, S{\"u}leyman},
  title     = {Bone marrow-independent adventitial macrophage progenitor cells contribute to angiogenesis},
  series = {Cell Death \& Disease},
  volume    = {13},
  journal   = {Cell Death \& Disease},
  number    = {3},
  doi       = {10.1038/s41419-022-04605-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299724},
  year      = {2022},
  abstract  = {Pathological angiogenesis promotes tumor growth, metastasis, and atherosclerotic plaque rupture. Macrophages are key players in these processes. However, whether these macrophages differentiate from bone marrow-derived monocytes or from local vascular wall-resident stem and progenitor cells (VW-SCs) is an unresolved issue of angiogenesis. To answer this question, we analyzed vascular sprouting and alterations in aortic cell populations in mouse aortic ring assays (ARA). ARA culture leads to the generation of large numbers of macrophages, especially within the aortic adventitia. Using immunohistochemical fate-mapping and genetic in vivo-labeling approaches we show that 60\% of these macrophages differentiate from bone marrow-independent Ly6c\(^{+}\)/Sca-1\(^{+}\) adventitial progenitor cells. Analysis of the NCX\(^{-/-}\) mouse model that genetically lacks embryonic circulation and yolk sac perfusion indicates that at least some of those progenitor cells arise yolk sac-independent. Macrophages represent the main source of VEGF in ARA that vice versa promotes the generation of additional macrophages thereby creating a pro-angiogenetic feedforward loop. Additionally, macrophage-derived VEGF activates CD34\(^{+}\) progenitor cells within the adventitial vasculogenic zone to differentiate into CD31\(^{+}\) endothelial cells. Consequently, depletion of macrophages and VEGFR2 antagonism drastically reduce vascular sprouting activity in ARA. In summary, we show that angiogenic activation induces differentiation of macrophages from bone marrow-derived as well as from bone marrow-independent VW-SCs. The latter ones are at least partially yolk sac-independent, too. Those VW-SC-derived macrophages critically contribute to angiogenesis, making them an attractive target to interfere with pathological angiogenesis in cancer and atherosclerosis as well as with regenerative angiogenesis in ischemic cardiovascular disorders.},
  language  = {en}
}
@article{KleefeldtBoemmelBroedeetal.2019,
  author    = {Kleefeldt, Florian and B{\"o}mmel, Heike and Broede, Britta and Thomsen, Michael and Pfeiffer, Verena and W{\"o}rsd{\"o}rfer, Philipp and Karnati, Srikanth and Wagner, Nicole and Rueckschloss, Uwe and Erg{\"u}n, S{\"u}leyman},
  title     = {Aging-related carcinoembryonic antigen-related cell adhesion molecule 1 signaling promotes vascular dysfunction},
  series = {Aging Cell},
  volume    = {2019},
  journal   = {Aging Cell},
  number    = {18},
  doi       = {10.1111/acel.13025},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201231},
  pages     = {e13025},
  year      = {2019},
  abstract  = {Aging is an independent risk factor for cardiovascular diseases and therefore of particular interest for the prevention of cardiovascular events. However, the mechanisms underlying vascular aging are not well understood. Since carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is crucially involved in vascular homeostasis, we sought to identify the role of CEACAM1 in vascular aging. Using human internal thoracic artery and murine aorta, we show that CEACAM1 is upregulated in the course of vascular aging. Further analyses demonstrated that TNF-α is CEACAM1-dependently upregulated in the aging vasculature. Vice versa, TNF-α induces CEACAM1 expression. This results in a feed-forward loop in the aging vasculature that maintains a chronic pro-inflammatory milieu. Furthermore, we demonstrate that age-associated vascular alterations, that is, increased oxidative stress and vascular fibrosis, due to increased medial collagen deposition crucially depend on the presence of CEACAM1. Additionally, age-dependent upregulation of vascular CEACAM1 expression contributes to endothelial barrier impairment, putatively via increased VEGF/VEGFR-2 signaling. Consequently, aging-related upregulation of vascular CEACAM1 expression results in endothelial dysfunction that may promote atherosclerotic plaque formation in the presence of additional risk factors. Our data suggest that CEACAM1 might represent an attractive target in order to delay physiological aging and therefore the transition to vascular disorders such as atherosclerosis.},
  language  = {en}
}