Efthymios Paronis1,2,3, Michalis Katsimpoulas1, Nikolaos P E Kadoglou4, Claire Provost5, Marianna Stasinopoulou1, Christos Spyropoulos6, Elpida Poulaki7, Aurelie Prignon5, Ioannis Kakisis2, Nikolaos G Kostomitsopoulos1, Penelope Bouziotis8, Ioannis V Kostopoulos3, Ourania Tsitsilonis3, Andreas Lazaris2. 1. Center of Clinical, Experimental Surgery & Translational Research, Biomedical Research Foundation, Academy of Athens (BRFAA), Athens, Greece. 2. Vascular Surgery Department, School of Medicine, National and Kapodistrian University of Athens, Attikon Teaching Hospital, Athens, Greece. 3. Section of Animal and Human Physiology, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Ilissia, Athens, Greece. 4. Center for Statistics in Medicine-Botnar Research Centre, University of Oxford, Oxford, United Kingdom. 5. Sorbonne University, UMS28, plateforme LIMP, Laboratoire d'Imagerie Moléculaire Positonique, Hopital Tenon, Paris, France. 6. Institute of Energy, Safety and Environmental Technologies, National Center for Scientific Research "Demokritos," Athens, Greece. 7. First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. 8. Radiochemical Studies Laboratory, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center for Scientific Research "Demokritos," Athens, Greece.
Abstract
BACKGROUND: Cilostazol is a drug of choice for the treatment of intermittent claudication that also affects innate and adaptive immune cells. The purpose of our study was the evaluation of cilostazol's impact on the immune and angiogenic response in murine models of hind limb ischemia. METHODS: We used 108 immunodeficient NOD.CB17-Prkdcscid/J mice and 108 wild-type CB17 mice. At day 0 (D0), all animals underwent hind limb ischemia. Half of them in both groups received daily cilostazol starting at D0 and for the next 7 postoperative days, while the rest of them served as controls, receiving vehicle. Interleukin (IL) 2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ) serum concentrations were measured by flow cytometry on postsurgery days D1, D3, D5, and D7. On D7, both groups underwent positron emission tomography scan with 68Ga-RGD. Mice were euthanatized and gastrocnemius muscles were obtained for histological evaluation. RESULTS: There was a statistically significant augmentation (P < .05) in IL-4, IL-10, IL-6, and IFN-γ concentrations in treated CB17 animals, while IL-2 was significantly suppressed. Significant difference was detected between the CiBisch and Bisch groups on D1 and D7 (P < .05) in CD31 staining. In treated NOD.CB17 animals, TNF-α, IL-6, and IFN-γ presented significant augmentation, while 68Ga-NODAGA-RGDfK uptake and CD31 expression were found significantly lower for both legs in comparison to the control. CONCLUSION: Cilostazol seems to significantly increase angiogenesis in wild-type animals during the first postoperational week. It also influences immune cells, altering the type of immune response by promoting anti-inflammatory cytokine production in wild-type animals, while it helps toward inflammation regression in immunodeficient animals.
BACKGROUND:Cilostazol is a drug of choice for the treatment of intermittent claudication that also affects innate and adaptive immune cells. The purpose of our study was the evaluation of cilostazol's impact on the immune and angiogenic response in murine models of hind limb ischemia. METHODS: We used 108 immunodeficient NOD.CB17-Prkdcscid/J mice and 108 wild-type CB17 mice. At day 0 (D0), all animals underwent hind limb ischemia. Half of them in both groups received daily cilostazol starting at D0 and for the next 7 postoperative days, while the rest of them served as controls, receiving vehicle. Interleukin (IL) 2, IL-4, IL-6, IL-10, IL-17A, tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ) serum concentrations were measured by flow cytometry on postsurgery days D1, D3, D5, and D7. On D7, both groups underwent positron emission tomography scan with 68Ga-RGD. Mice were euthanatized and gastrocnemius muscles were obtained for histological evaluation. RESULTS: There was a statistically significant augmentation (P < .05) in IL-4, IL-10, IL-6, and IFN-γ concentrations in treated CB17 animals, while IL-2 was significantly suppressed. Significant difference was detected between the CiBisch and Bisch groups on D1 and D7 (P < .05) in CD31 staining. In treated NOD.CB17 animals, TNF-α, IL-6, and IFN-γ presented significant augmentation, while 68Ga-NODAGA-RGDfK uptake and CD31 expression were found significantly lower for both legs in comparison to the control. CONCLUSION:Cilostazol seems to significantly increase angiogenesis in wild-type animals during the first postoperational week. It also influences immune cells, altering the type of immune response by promoting anti-inflammatory cytokine production in wild-type animals, while it helps toward inflammation regression in immunodeficient animals.
Authors: Mustafa Etli; Oğuz Karahan; Özgür Akkaya; Hasan Basri Savaş Journal: Turk Gogus Kalp Damar Cerrahisi Derg Date: 2021-10-20 Impact factor: 0.332