Cilostazol stimulates revascularisation in response to ischaemia via an eNOS-dependent mechanism
A. Hori, R. Shibata, K. Morisaki, T. Murohara, K. Komori
Objectives: Cilostazol is known to be a selective inhibitor of phosphodiesterase 3 and is generally used to treat intermittent claudication caused by peripheral arterial disease. However, there is little information concerning the effect of cilostazol on angiogenesis. Here, we investigated whether cilostazol modulates the angiogenic process in vivo employing a hindlimb model of ischaemia-induced angiogenesis. Design: This was an experimental study. Materials and methods: Wild-type (WT) mice were randomly divided into two groups and were treated with or without cilostazol. One week later, the mice were subjected to unilateral hindlimb ischaemia. Angiogenesis was determined by laser Doppler analysis and capillary density stained with CD31. The expression of endothelial nitric oxide synthase (eNOS) was assessed by immunoblotting. Results: WT mice treated with cilostazol showed accelerated neo-vascularisation following hindlimb ischaemic surgery on post-operative day 14 based upon laser Doppler measurements of blood flow (cilostazol-treated group, 0.54 ± 0.13 vs. control group, 0.38 ± 0.11; P-<-0.05). The capillary density in the ischaemic hindlimb was also significantly greater in WT mice treated with cilostazol than in non-treated WT mice (cilostazol-treated group, 1.63 ± 0.10 vs. control group, 1.15 ± 0.12; P-<-0.01). Cilostazol stimulated an ischaemia-induced increase in the phosphorylation of eNOS in the ischaemic limbs. Administration of NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME) abolished cilostazol-induced increase in limb perfusion. Conclusions: Our observations indicate that cilostazol can promote neo-vascularisation in response to tissue ischaemia via an eNOS-dependent mechanism. Cilostazol could be useful for treatment of ischaemic limb diseases.
European Journal of Vascular and Endovascular Surgery
https://doi.org/10.1016/j.ejvs.2011.07.015
10.1016/j.ejvs.2011.07.015
Dive into the research topics of 'Cilostazol stimulates revascularisation in response to ischaemia via an eNOS-dependent mechanism'. Together they form a unique fingerprint.
Cilostazol Pharmacology, Toxicology and Pharmaceutical Science 100%
Ischemia Pharmacology, Toxicology and Pharmaceutical Science 38%
Wild Type Mouse Pharmacology, Toxicology and Pharmaceutical Science 30%
Endothelial Nitric Oxide Synthase Pharmacology, Toxicology and Pharmaceutical Science 30%
Angiogenesis Neuroscience 23%
Western Blot Pharmacology, Toxicology and Pharmaceutical Science 15%
Neovascularization (Pathology) Pharmacology, Toxicology and Pharmaceutical Science 15%
Mouse Pharmacology, Toxicology and Pharmaceutical Science 7%
Hori, A., Shibata, R., Morisaki, K., Murohara, T., & Komori, K. (2012). Cilostazol stimulates revascularisation in response to ischaemia via an eNOS-dependent mechanism. European Journal of Vascular and Endovascular Surgery, 43(1), 62-65. https://doi.org/10.1016/j.ejvs.2011.07.015
Cilostazol stimulates revascularisation in response to ischaemia via an eNOS-dependent mechanism. / Hori, A.; Shibata, R.; Morisaki, K. et al.
In: European Journal of Vascular and Endovascular Surgery, Vol. 43, No. 1, 01.2012, p. 62-65.
Hori, A, Shibata, R, Morisaki, K, Murohara, T & Komori, K 2012, 'Cilostazol stimulates revascularisation in response to ischaemia via an eNOS-dependent mechanism', European Journal of Vascular and Endovascular Surgery, vol. 43, no. 1, pp. 62-65. https://doi.org/10.1016/j.ejvs.2011.07.015
Hori A, Shibata R, Morisaki K, Murohara T, Komori K. Cilostazol stimulates revascularisation in response to ischaemia via an eNOS-dependent mechanism. European Journal of Vascular and Endovascular Surgery. 2012 Jan;43(1):62-65. doi: 10.1016/j.ejvs.2011.07.015
Hori, A. ; Shibata, R. ; Morisaki, K. et al. / Cilostazol stimulates revascularisation in response to ischaemia via an eNOS-dependent mechanism. In: European Journal of Vascular and Endovascular Surgery. 2012 ; Vol. 43, No. 1. pp. 62-65.
@article{074d94e1193041068d2ecace9191f4c5,
title = "Cilostazol stimulates revascularisation in response to ischaemia via an eNOS-dependent mechanism",
abstract = "Objectives: Cilostazol is known to be a selective inhibitor of phosphodiesterase 3 and is generally used to treat intermittent claudication caused by peripheral arterial disease. However, there is little information concerning the effect of cilostazol on angiogenesis. Here, we investigated whether cilostazol modulates the angiogenic process in vivo employing a hindlimb model of ischaemia-induced angiogenesis. Design: This was an experimental study. Materials and methods: Wild-type (WT) mice were randomly divided into two groups and were treated with or without cilostazol. One week later, the mice were subjected to unilateral hindlimb ischaemia. Angiogenesis was determined by laser Doppler analysis and capillary density stained with CD31. The expression of endothelial nitric oxide synthase (eNOS) was assessed by immunoblotting. Results: WT mice treated with cilostazol showed accelerated neo-vascularisation following hindlimb ischaemic surgery on post-operative day 14 based upon laser Doppler measurements of blood flow (cilostazol-treated group, 0.54 ± 0.13 vs. control group, 0.38 ± 0.11; P-<-0.05). The capillary density in the ischaemic hindlimb was also significantly greater in WT mice treated with cilostazol than in non-treated WT mice (cilostazol-treated group, 1.63 ± 0.10 vs. control group, 1.15 ± 0.12; P-<-0.01). Cilostazol stimulated an ischaemia-induced increase in the phosphorylation of eNOS in the ischaemic limbs. Administration of NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME) abolished cilostazol-induced increase in limb perfusion. Conclusions: Our observations indicate that cilostazol can promote neo-vascularisation in response to tissue ischaemia via an eNOS-dependent mechanism. Cilostazol could be useful for treatment of ischaemic limb diseases.",
author = "A. Hori and R. Shibata and K. Morisaki and T. Murohara and K. Komori",
note = "Funding Information: This work was supported in part by a grant-in-aid for General Scientific Research from the Ministry of Education, Science and Culture of Japan 21390357 . ",
doi = "10.1016/j.ejvs.2011.07.015",
journal = "European Journal of Vascular and Endovascular Surgery",
T1 - Cilostazol stimulates revascularisation in response to ischaemia via an eNOS-dependent mechanism
AU - Hori, A.
AU - Shibata, R.
AU - Morisaki, K.
AU - Murohara, T.
AU - Komori, K.
N1 - Funding Information: This work was supported in part by a grant-in-aid for General Scientific Research from the Ministry of Education, Science and Culture of Japan 21390357 .
N2 - Objectives: Cilostazol is known to be a selective inhibitor of phosphodiesterase 3 and is generally used to treat intermittent claudication caused by peripheral arterial disease. However, there is little information concerning the effect of cilostazol on angiogenesis. Here, we investigated whether cilostazol modulates the angiogenic process in vivo employing a hindlimb model of ischaemia-induced angiogenesis. Design: This was an experimental study. Materials and methods: Wild-type (WT) mice were randomly divided into two groups and were treated with or without cilostazol. One week later, the mice were subjected to unilateral hindlimb ischaemia. Angiogenesis was determined by laser Doppler analysis and capillary density stained with CD31. The expression of endothelial nitric oxide synthase (eNOS) was assessed by immunoblotting. Results: WT mice treated with cilostazol showed accelerated neo-vascularisation following hindlimb ischaemic surgery on post-operative day 14 based upon laser Doppler measurements of blood flow (cilostazol-treated group, 0.54 ± 0.13 vs. control group, 0.38 ± 0.11; P-<-0.05). The capillary density in the ischaemic hindlimb was also significantly greater in WT mice treated with cilostazol than in non-treated WT mice (cilostazol-treated group, 1.63 ± 0.10 vs. control group, 1.15 ± 0.12; P-<-0.01). Cilostazol stimulated an ischaemia-induced increase in the phosphorylation of eNOS in the ischaemic limbs. Administration of NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME) abolished cilostazol-induced increase in limb perfusion. Conclusions: Our observations indicate that cilostazol can promote neo-vascularisation in response to tissue ischaemia via an eNOS-dependent mechanism. Cilostazol could be useful for treatment of ischaemic limb diseases.
AB - Objectives: Cilostazol is known to be a selective inhibitor of phosphodiesterase 3 and is generally used to treat intermittent claudication caused by peripheral arterial disease. However, there is little information concerning the effect of cilostazol on angiogenesis. Here, we investigated whether cilostazol modulates the angiogenic process in vivo employing a hindlimb model of ischaemia-induced angiogenesis. Design: This was an experimental study. Materials and methods: Wild-type (WT) mice were randomly divided into two groups and were treated with or without cilostazol. One week later, the mice were subjected to unilateral hindlimb ischaemia. Angiogenesis was determined by laser Doppler analysis and capillary density stained with CD31. The expression of endothelial nitric oxide synthase (eNOS) was assessed by immunoblotting. Results: WT mice treated with cilostazol showed accelerated neo-vascularisation following hindlimb ischaemic surgery on post-operative day 14 based upon laser Doppler measurements of blood flow (cilostazol-treated group, 0.54 ± 0.13 vs. control group, 0.38 ± 0.11; P-<-0.05). The capillary density in the ischaemic hindlimb was also significantly greater in WT mice treated with cilostazol than in non-treated WT mice (cilostazol-treated group, 1.63 ± 0.10 vs. control group, 1.15 ± 0.12; P-<-0.01). Cilostazol stimulated an ischaemia-induced increase in the phosphorylation of eNOS in the ischaemic limbs. Administration of NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME) abolished cilostazol-induced increase in limb perfusion. Conclusions: Our observations indicate that cilostazol can promote neo-vascularisation in response to tissue ischaemia via an eNOS-dependent mechanism. Cilostazol could be useful for treatment of ischaemic limb diseases.
U2 - 10.1016/j.ejvs.2011.07.015
DO - 10.1016/j.ejvs.2011.07.015
JO - European Journal of Vascular and Endovascular Surgery
JF - European Journal of Vascular and Endovascular Surgery