Cilostazol Mediates Immune Responses and Affects Angiogenesis During the Acute Phase of Hind Limb Ischemia in a Mouse Model.
Angiogenesis Inducing Agents
/ pharmacology
Animals
Cilostazol
/ pharmacology
Cytokines
/ blood
Disease Models, Animal
Hindlimb
Immunity, Innate
/ drug effects
Immunocompromised Host
Inflammation Mediators
/ blood
Ischemia
/ drug therapy
Male
Mice, Inbred NOD
Mice, SCID
Muscle, Skeletal
/ blood supply
Neovascularization, Physiologic
/ drug effects
Signal Transduction
angiogenesis
cilostazol
cytokine profile
mouse model
peripheral ischemia
Journal
Journal of cardiovascular pharmacology and therapeutics
ISSN: 1940-4034
Titre abrégé: J Cardiovasc Pharmacol Ther
Pays: United States
ID NLM: 9602617
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
pubmed:
8
1
2020
medline:
7
10
2020
entrez:
8
1
2020
Statut:
ppublish
Résumé
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. 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 There was a statistically significant augmentation ( 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.
Sections du résumé
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
RESULTS
There was a statistically significant augmentation (
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.
Identifiants
pubmed: 31906705
doi: 10.1177/1074248419897852
doi:
Substances chimiques
Angiogenesis Inducing Agents
0
Cytokines
0
Inflammation Mediators
0
Cilostazol
N7Z035406B
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM