TY - GEN A1 - Lau, S. A1 - Rangarajan, R. A1 - Krüger-Genge, Anne A1 - Braune, Steffen A1 - Küpper, Jan-Heiner A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Age-related morphology and function of human arterial endothelial cells T2 - Clinical Hemorheology and Microcirculation N2 - Endothelialization of cardiovascular implants is regarded as a promising strategy for long-term compatibility. While umbilical vein endothelial cells are typically applied in research, human arterial endothelial cells (HAEC) from elderly donors would be the obvious source for autologous cellularization strategies. In our approach, HAEC from 16 donors of varying age (16–63 years) were divided into two groups (<30 years and >30 years) and analyzed regarding morphology, viability, proliferation, function and senescence status. No age-related differences were found regarding morphology, viability, density, prostacyclin and nitrite secretion or collagen and laminin production. However, the metabolic activity was slightly decreased (p = 0.0374) and the membrane integrity marginally impaired (p = 0.0404) in cells from older donors. Two out of three senescence assays detected more senescence markers in cells from older donors. According to the assays applied here, HAEC from young and elderly donors up to the age of 63 years could be judged equally suitable for autologous cellularization strategies. However, this finding should be regarded with caution due to the extremely large variability between individual donors. Further studies comprising a larger sample size are necessary to investigate this issue more thoroughly. KW - Cardiovascular implants KW - arterial endothelial cells KW - aging KW - senescence KW - donor variability Y1 - 2020 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch199238 U6 - https://doi.org/10.3233/CH-199238 SN - 1875-8622 SN - 1386-0291 VL - 74 IS - 1 SP - 93 EP - 107 ER - TY - GEN A1 - Jung, Friedrich A1 - Connes, Philippe A1 - Lehmann, Christian T1 - A.L. Copley Best Paper Prize 2020 T2 - Clinical Hemorheology and Microcirculation Y1 - 2021 UR - https://europepmc.org/article/med/33720877 U6 - https://doi.org/10.3233/ch-219001 SN - 1875-8622 SN - 1386-0291 VL - 77 IS - 3 SP - 245 EP - 246 ER - TY - GEN A1 - Schulz, Christian A1 - Krüger-Genge, Anne A1 - Lendlein, Andreas A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Potential Effects of Nonadherent on Adherent Human Umbilical Venous Endothelial Cells in Cell Culture T2 - International Journal of Molecular Science N2 - The adherence and shear-resistance of human umbilical venous endothelial cells (HUVEC) on polymers is determined in vitro in order to qualify cardiovascular implant materials. In these tests, variable fractions of HUVEC do not adhere to the material but remain suspended in the culture medium. Nonadherent HUVEC usually stop growing, rapidly lose their viability and can release mediators able to influence the growth and function of the adherent HUVEC. The aim of this study was the investigation of the time dependent behaviour of HUVEC under controlled nonadherent conditions, in order to gain insights into potential influences of these cells on their surrounding environment in particular adherent HUVEC in the context of in vitro biofunctionality assessment of cardiovascular implant materials. Data from adherent or nonadherent HUVEC growing on polystyrene-based cell adhesive tissue culture plates (TCP) or nonadhesive low attachment plates (LAP) allow to calculate the number of mediators released into the culture medium either from adherent or nonadherent cells. Thus, the source of the inflammatory mediators can be identified. For nonadherent HUVEC, a time-dependent aggregation without further proliferation was observed. The rate of apoptotic/dead HUVEC progressively increased over 90% within two days. Concomitant with distinct blebbing and loss of membrane integrity over time, augmented releases of prostacyclin (PGI2, up to 2.91 ± 0.62 fg/cell) and platelet-derived growth factor BB (PDGF-BB, up to 1.46 ± 0.42 fg/cell) were detected. The study revealed that nonadherent, dying HUVEC released mediators, which can influence the surrounding microenvironment and thereby the results of in vitro biofunctionality assessment of cardiovascular implant materials. Neglecting nonadherent HUVEC bears the risk for under- or overestimation of the materials endothelialization potential, which could lead to the loss of relevant candidates or to uncertainty with regard to their suitability for cardiac applications. One approach to minimize the influence from nonadherent endothelial cells could be their removal shortly after observing initial cell adhesion. However, this would require an individual adaptation of the study design, depending on the properties of the biomaterial used. KW - human venous endothelial cells KW - adherent KW - non-adherent KW - viability KW - mediator release Y1 - 2021 UR - https://www.mdpi.com/1422-0067/22/3/1493 U6 - https://doi.org/10.3390/ijms22031493 VL - 22 IS - 3 ER - TY - GEN A1 - Wiggermann, P. A1 - Krüger-Genge, Anne A1 - Jung, Friedrich T1 - Editorial T2 - Selected papers of the 38th Conference of the German Society for Clinical Microcirculation and Hemorheology, 21-23 November 2019, Braunschweig, Germany Y1 - 2019 UR - https://pubmed.ncbi.nlm.nih.gov/31561330/#affiliation-3 U6 - https://doi.org/10.3233/CH-199200 VL - 73 IS - 1 PB - IOS Press ER - TY - GEN A1 - Biermann, Niklas A1 - Sommerauer, Laura A1 - Diesch, Sophia A1 - Koch, Christoph A1 - Jung, Friedrich A1 - Kehrer, Andreas A1 - Prantl, Lukas A1 - Taeger, Christian D. T1 - The influence of pulsed electromagnetic field therapy (PEMFT) on cutaneous blood flow in healthy volunteers T2 - Clinical Hemorheology and Microcirculation N2 - BACKGROUND: The biophysical interaction induced by low energy pulsed electromagnetic field therapy (PEMFT) on the capillary microcirculation is not well understood. Several studies indicate a significant effect of PEMFT in patients with chronic medical conditions. OBJECTIVE: The aim of this study was to evaluate the influence of PEMFT on skin microcirculation in healthy volunteers. METHODS: 15 healthy participants were included. Nine PEMF treatments were applied over three weeks in an 48-hour interval. The PEMFT system (BEMER) was placed beneath one of the participants’ leg with the contralateral side serving as a control. A forty-minute application period was preceded by a 10-minute resting phase. Measuring was done using two Laser Doppler probes (LEA) placed on each anterior lateral thigh. RESULTS: All outcome parameters including flow, mixed venous oxygen saturation and relative venous hemoglobin showed a significant increase during the experiment when compared to the baseline values of the resting phase in both groups (p < 0.01). Comparing both groups, the measurement values during the experiment did not differ (p > 0.05) except for higher flow values in the control group (P = 0.03). Over time, baseline values of both groups showed no significant difference (p > 0.05). CONCLUSION: We found a significant increase of all measurement parameters during the study compared to the baseline values with no difference between the PEMF and control group. KW - Pulsed electromagnetic field therapy (PEMFT) KW - microcirculation KW - cutaneous blood flow Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch209224 U6 - https://doi.org/10.3233/CH-209224 VL - 76 IS - 4 SP - 495 EP - 501 ER - TY - GEN A1 - Braune, Steffen A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Effect of Prostanoids on Human Platelet Function: An Overview T2 - International Journal of Molecular Science N2 - Prostanoids are bioactive lipid mediators and take part in many physiological and pathophysiological processes in practically every organ, tissue and cell, including the vascular, renal, gastrointestinal and reproductive systems. In this review, we focus on their influence on platelets, which are key elements in thrombosis and hemostasis. The function of platelets is influenced by mediators in the blood and the vascular wall. Activated platelets aggregate and release bioactive substances, thereby activating further neighbored platelets, which finally can lead to the formation of thrombi. Prostanoids regulate the function of blood platelets by both activating or inhibiting and so are involved in hemostasis. Each prostanoid has a unique activity profile and, thus, a specific profile of action. This article reviews the effects of the following prostanoids: prostaglandin-D2 (PGD2), prostaglandin-E1, -E2 and E3 (PGE1, PGE2, PGE3), prostaglandin F2α (PGF2α), prostacyclin (PGI2) and thromboxane-A2 (TXA2) on platelet activation and aggregation via their respective receptors. Y1 - 2020 UR - https://www.mdpi.com/1422-0067/21/23/9020 U6 - https://doi.org/10.3390/ijms21239020 VL - 21 IS - 23 ER - TY - GEN A1 - Braune, Steffen A1 - Krüger-Genge, Anne A1 - Kammerer, Sarah A1 - Jung, Friedrich A1 - Küpper, Jan-Heiner T1 - Phycocyanin from Arthrospira platensis as Potential Anti-Cancer Drug: Review of In Vitro and In Vivo Studies T2 - Life Y1 - 2021 UR - https://www.mdpi.com/2075-1729/11/2/91 U6 - https://doi.org/10.3390/life11020091 VL - 11 IS - 2 SP - 91 ER - TY - GEN A1 - Taghizadeh, Mahmoudreza A1 - Mehdi, Kargarfard A1 - Braune, Steffen A1 - Jung, Friedrich A1 - Mahmood, Naderi T1 - Long-term aerobic exercise training in type two diabetic patients alters the expression of miRNA-223 and its corresponding target, the P2RY12 receptor, attenuating platelet function T2 - Clinical Hemorheology and Microcirculation N2 - BACKGROUND: Type two diabetes mellitus (T2DM) patients are prone to develop atherothrombotic events due to platelet hyper-reactivity stemming from platelet miRNA-223 down-regulation and over-expression of its corresponding target, P2RY12. OBJECTIVE: The study sought to determine the effects of long-term aerobic training on the expression levels of miRNA-223 and P2RY12 mRNA, and platelet function in T2DM patients. METHODS: Twenty-four patients with T2DM (age, 60.0±2.8 yrs.) were selected and randomly divided into two groups: aerobic exercise training (AET, n = 12) and control (CON, n = 12). The AET protocol was performed with moderate intensity for 12 weeks, while patients in the CON group followed their usual routine. Weight, body mass index (BMI), peak oxygen consumption (VO2peak), lipid profile, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), insulin resistance index (HOMA-IR), platelet miRNA-223 and P2RY12 expression were measured before and after the period. RESULTS: There was a significant improvement in body weight, BMI, VO2peak, FBG, HbA1c, and HOMA-IR, after 12 weeks of AET (P <  0.01). Platelet aggregation decreased significantly after 12 weeks in the AET group compared with the CON (P <  0.001) group. Platelets’ miRNA-223 and P2RY12 were significantly up- and down-regulated after AET in comparison with the CON group (P <  0.05), respectively. Moreover, the relative expression of miRNA-223 and P2RY12 significantly correlated with FBG changes following the intervention. CONCLUSIONS: It can be concluded that long-term moderate-intensity aerobic training might be effective for reducing the occurrence of atherothrombotic events leading to premature death in T2DM patients through the modulation of miRNA-223, P2RY12 receptor expression, and platelet function. KW - Exercise training KW - diabetes KW - microRNA-223 KW - P2RY12 receptor KW - Insulin resistance KW - platelet Y1 - 2022 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch211209 U6 - https://doi.org/10.3233/CH-211209 SN - 1875-8622 SN - 1386-0291 VL - 80 IS - 2 SP - 107 EP - 116 ER - TY - GEN A1 - Greif, G. A1 - Mrowietz, Christof A1 - Wendt, M. A1 - Jung, Friedrich A1 - Hiebl, Bernhard A1 - Meyer-Sievers, H. T1 - Differences in human and minipig platelet number, volume and activation induced by borosilicate glass beads in a modified chandler loop-system T2 - Clinical Hemorheology and Microcirculation N2 - The pig is the most widely used large animal model in Europe, with cardiovascular research being one of the main areas of application. Adequate refinement of interventional studies in this field, meeting the requirements of Russel and Burchs’ 3 R concept, can only be performed if blood-contacting medical devices are hemocompatible. Because most medical devices for cardiovascular interventional procedures are developed for humans they are tested mostly for compatibility with human blood. The aim of this study was therefore to determine whether there are differences in behavior of porcine and human platelets when they come into contact with glass, which was used as an exemplary thrombogenic material. For this purpose changes of platelet count, platelet volume and platelet expression of the activation markers CD61, CD62P and CD63 were measured using a modified chandler loop-system simulating the fluidic effects of the blood flow. Minipig and human platelets showed significant differences in number and volume, but not in activation after 4–8 min exposure to glass. KW - Pig KW - minipig KW - platelet activation KW - platelet count KW - platelet volume KW - FACS KW - monoclonal antibody KW - CD42 KW - CD61 KW - CD62P KW - CD63 Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch219201 U6 - https://doi.org/10.3233/CH-219201 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 1 SP - 149 EP - 155 ER - TY - GEN A1 - Schulz, Christian A1 - Jung, Friedrich A1 - Küpper, Jan-Heiner T1 - Inhibition of phase-1 biotransformation and cytostatic effects of diphenyleneiodonium on hepatoblastoma cell line HepG2 and a CYP3A4-overexpressing HepG2 cell clone T2 - Clinical Hemorheology and Microcirculation N2 - Cell-based in vitro liver models are an important tool in the development and evaluation of new drugs in pharmacological and toxicological drug assessment. Hepatic microsomal enzyme complexes, consisting of cytochrome P450 oxidoreductase (CPR) and cytochrome P450 monooxygenases (CYPs), play a decisive role in catalysing phase-1 biotransformation of pharmaceuticals and xenobiotics. For a comprehensive understanding of the phase-1 biotransformation of drugs, the availability of well-characterized substances for the targeted modulation of in vitro liver models is essential. In this study, we investigated diphenyleneiodonium (DPI) for its ability to inhibit phase-1 enzyme activity and further its toxicological profile in an in vitro HepG2 cell model with and without recombinant expression of the most important drug metabolization enzyme CYP3A4. Aim of the study was to identify effective DPI concentrations for CPR/CYP activity modulation and potentially associated dose and time dependent hepatotoxic effects. The cells were treated with DPI doses up to 5,000nM (versus vehicle control) for a maximum of 48 h and subsequently examined for CYP3A4 activity as well as various toxicological relevant parameters such as cell morphology, integrity and viability, intracellular ATP level, and proliferation. Concluding, the experiments revealed a time- and concentration-dependent DPI mediated partial and complete inhibition of CYP3A4 activity in CYP3A4 overexpressing HepG2-cells (HepG2-CYP3A4). Other cell functions, including ATP synthesis and consequently the proliferation were negatively affected in both in vitro cell models. Since neither cell integrity nor cell viability were reduced, the effect of DPI in HepG2 can be assessed as cytostatic rather than cytotoxic. KW - Phase-1 KW - biotransformation KW - CYP KW - cytochrome P450 monooxygenase KW - CYP3A4 KW - diphenyleneiodonium KW - DPI KW - HepG2 KW - HepG2-CYP3A4 KW - hepatocytes KW - NADPH-cytochrome P450 oxidoreductase KW - POR KW - CPR Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch219117 U6 - https://doi.org/10.3233/CH-219117 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 1 SP - 231 EP - 243 ER - TY - GEN A1 - Greif, G. A1 - Mrowietz, Christof A1 - Meyer-Sievers, H. A1 - Ganter, M. A1 - Jung, Friedrich A1 - Hiebl, Bernhard T1 - Differences in human and sheep platelet adherence, aggregation and activation induced by glass beads in a modified chandler loop-system T2 - Clinical Hemorheology and Microcirculation N2 - In human cardiovascular research, sheep in particular are used as a large animal model in addition to pigs. In these animals, medical products, developed and tested for human medical purposes, are almost exclusively used in interventional studies. Therefore, the extent to which platelets from human and ovine blood differ in terms of adherence, aggregation and activation after a 4- or 8-minutes exposure to glass was investigated. Testing was performed with platelet-rich plasma (PRP) and a modified chandler loop-system, with 4- and 8-minute blood-material exposure times corresponding to 20 and 40 test cycles, respectively, through the entire silicone tube loop of the test system. In sheep and human PRP, contact with the silicone tubing resulted in a decrease in platelet count after 4 minutes and 20 test cycles, respectively. Four more minutes (20 additional test cycles) caused a further decrease of the platelet count only in sheep PRP. When the silicon tube was partly filled with glass beads, these effects were more pronounced and stronger in sheep then in human PRP. The mean platelet volume, which was used as parameter for platelet aggregation, did not change over time in human PRP without glass exposure. With glass exposure in human and sheep PRP the mean platelet volume increased within 40 test cycles, but this increase was stronger in sheep than in human PRP. Regarding activation behavior, the activation markers CD62P and CD63 were detectable only in < 30% (sheep) and < 45% (human) of platelets, whereas after 8 min of glass exposure, the proportion of CD62P+ and CD63+ cells was more increased than before only in sheep. These results indicate that ovine platelets adhere more strongly to glass and show stronger aggregation behavior after glass contact than human platelets, but that ovine and human platelets differ only slightly in activability by glass. KW - Sheep KW - platelet KW - activation KW - platelet volume KW - CD42a KW - CD61 KW - CD62P KW - CD63 Y1 - 2021 UR - https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch219104 U6 - https://doi.org/10.3233/CH-219104 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 1 SP - 129 EP - 136 ER - TY - GEN A1 - Küpper, Jan-Heiner A1 - Krüger-Genge, Anne A1 - Jung, Friedrich T1 - 40th conference of the German society for clinical microcirculation and hemorheology (DGKMH) T2 - Clinical Hemorheology and Microcirculation Y1 - 2021 U6 - https://doi.org/10.3233/ch-219100 SN - 1875-8622 SN - 1386-0291 VL - 79 IS - 1 SP - 1 EP - 2 ER - TY - PAT A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Arthrospira for use in the treatment of diseases Y1 - 2021 UR - https://www.google.de/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwik1t7QrOL5AhVTO-wKHT97CKAQFnoECAQQAQ&url=https%3A%2F%2Fdata.epo.org%2Fpublication-server%2Frest%2Fv1.0%2Fpublication-dates%2F20220302%2Fpatents%2FEP3960193NWA1%2Fdocument.pdf&usg=AOvVaw20GVY_ywjb2xbS0TwSDArJ ER - TY - PAT A1 - Scheibner, Katrin A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - In vitro Arzneimittel aus Prodrugs und deren Verwendung Y1 - 2021 UR - https://www.b-tu.de/enzymtechnologie/publikationen/patente ER - TY - GEN A1 - Tartivel, Lucile A1 - Blocki, Anna M. A1 - Braune, Steffen A1 - Jung, Friedrich A1 - Behl, Marc A1 - Lendlein, Andreas T1 - An Inverse Shape-Memory Hydrogel Scaffold Switching Upon Cooling in a Tissue-Tolerated Temperature Range T2 - Advanced materials interfaces Y1 - 2022 U6 - https://doi.org/10.1002/admi.202101588 SN - 2196-7350 VL - 9 IS - 6 ER - TY - GEN A1 - Lau, S. A1 - Gossen, Maike A1 - Lendlein, Andreas A1 - Jung, Friedrich T1 - Differential sensitivity of assays for determining vein endothelial cell senescence T2 - Clinical Hemorheology and Microcirculation Y1 - 2022 U6 - https://doi.org/10.3233/CH-211294 SN - 1875-8622 SN - 1386-0291 VL - 81 IS - 3 SP - 191 EP - 203 ER - TY - GEN A1 - Lemm, Sandy A1 - Köhler, Susanne A1 - Wodtke, Robert A1 - Jung, Friedrich A1 - Küpper, Jan-Heiner A1 - Pietzsch, Jens A1 - Laube, Markus T1 - Investigation of radiotracer metabolic stability in vitro with CYP-overexpressing hepatoma cell lines T2 - Cells Y1 - 2022 U6 - https://doi.org/10.3390/cells11152447 SN - 2073-4409 VL - 11 IS - 15 ER - TY - GEN A1 - Jung, Friedrich A1 - Connes, Philippe A1 - Lehmann, Christian T1 - A.L. Copley Best Paper Prize 2021 T2 - Clinical Hemorheology and Microcirculation Y1 - 2022 U6 - https://doi.org/10.3233/CH-229901 SN - 1875-8622 SN - 1386-0291 VL - 82 IS - 3 SP - 199 EP - 200 ER - TY - GEN A1 - Braune, Steffen A1 - Krüger-Genge, Anne A1 - Köhler, S. A1 - Küpper, Jan-Heiner A1 - Jung, Friedrich T1 - Effects of Arthrospira platensis-derived substances on blood cells T2 - Clinical Hemorheology and Microcirculation Y1 - 2022 U6 - https://doi.org/10.3233/CH-229103 SN - 1875-8622 VL - 85(2023) IS - 3 SP - 315 EP - 321 ER - TY - GEN A1 - Lemm, Sandy A1 - Köhler, Susanne A1 - Wodtke, Robert A1 - Jung, Friedrich A1 - Küpper, Jan-Heiner A1 - Pietzsch, Jens A1 - Laube, Markus T1 - Enabling insights into the cytochrome P450 isoform specific metabolism of radiotracers by CYP overexpressing hepatoblastoma cell lines T2 - Nuclear Medicine and Biology Y1 - 2022 SN - 1872-9614 IS - 108-109, Supplement  SP - S66 EP - S67 ER - TY - GEN A1 - Jung, Friedrich A1 - Connes, Philippe T1 - Morphology and Function of Red Blood Cells in COVID-19 Patients: Current Overview 2023 T2 - Life N2 - In severe cases, SARS-CoV-2 infection leads to severe respiratory failure. Although angiotensin-converting enzyme 2 (ACE2) receptors are not expressed in red blood cells, SARS-CoV-2 can interact with red blood cells (RBCs) via several receptors or auxiliary membrane proteins. Recent data show that viral infection causes significant damage to the RBCs, altering their morphology, deformability, and aggregability. Loss of RBC deformability and/or increased aggregability favors the development of thrombotic processes in the microcirculation, as has been described to occur in COVID-19 patients. In addition, many patients also develop systemic endotheliitis associated with generalized coagulopathy. This manifests itself clinically as obstructive microthrombi in the area of the medium and smallest vessels, which can affect all internal organs. It is thought that such changes in the RBCs may contribute to the microangiopathy/microthrombosis associated with COVID-19 and may result in impaired capillary blood flow and tissue oxygenation. KW - COVID-19 KW - SARS-CoV-2 KW - red blood cell KW - deformation KW - aggregation KW - endothelial cell Y1 - 2024 U6 - https://doi.org/10.3390/life14040460 SN - 2075-1729 VL - 14 IS - 4 ER -