Τίτλος:
Cilostazol Mediates Immune Responses and Affects Angiogenesis During the Acute Phase of Hind Limb Ischemia in a Mouse Model
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © The Author(s) 2020.
Συγγραφείς:
Paronis, E.
Katsimpoulas, M.
Kadoglou, N.P.E.
Provost, C.
Stasinopoulou, M.
Spyropoulos, C.
Poulaki, E.
Prignon, A.
Kakisis, I.
Kostomitsopoulos, N.G.
Bouziotis, P.
Kostopoulos, I.V.
Tsitsilonis, O.
Lazaris, A.
Περιοδικό:
Journal of Cardiovascular Pharmacology and Therapeutics
Εκδότης:
SAGE Publications Ltd
Λέξεις-κλειδιά:
cilostazol; gamma interferon; interleukin 10; interleukin 17; interleukin 2; interleukin 4; interleukin 6; platelet endothelial cell adhesion molecule 1; tumor necrosis factor; angiogenic factor; autacoid; cilostazol; cytokine, angiogenesis; animal experiment; animal model; animal tissue; Article; CB17 mouse; clinical effectiveness; controlled study; cytokine production; drug effect; drug efficacy; drug mechanism; drug response; flow cytometry; gastrocnemius muscle; histology; immune response; limb ischemia; male; mouse; nonhuman; positron emission tomography; postoperative period; priority journal; protein expression; wild type; angiogenesis; animal; blood; comparative study; disease model; drug effect; hindlimb; immunocompromised patient; immunology; innate immunity; ischemia; metabolism; nonobese diabetic mouse; pathophysiology; SCID mouse; signal transduction; skeletal muscle; vascularization, Angiogenesis Inducing Agents; Animals; Cilostazol; Cytokines; Disease Models, Animal; Hindlimb; Immunity, Innate; Immunocompromised Host; Inflammation Mediators; Ischemia; Male; Mice, Inbred NOD; Mice, SCID; Muscle, Skeletal; Neovascularization, Physiologic; Signal Transduction
DOI:
10.1177/1074248419897852
