Anti-Inflammatory Role of Cilostazol in Vascular Smooth Muscle Cells In vitro and In vivo

Aoki, Chie; Hattori, Yoshiyuki; Tomizawa, Atsuko; Jojima, Teruo; Kasai, Kikuo

doi:10.5551/jat.3392

Cited by 48 publications

(45 citation statements)

References 14 publications

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“…In the current study, we used 1 dose of cilostazol. Because both antiplatelet and vasculoprotective activity of cilostazol are known to be dose-dependent, [52][53][54] further study will be necessary to determine the optimal dose of cilostazol to suppress cerebral hemorrhage after tPA treatment.…”

Section: Kasahara Et Al Cilostazol and Tpa-induced Hemorrhage 503mentioning

confidence: 99%

Cilostazol Reduces the Risk of Hemorrhagic Infarction After Administration of Tissue-Type Plasminogen Activator in a Murine Stroke Model

Kasahara

Nakagomi

Matsuyama

et al. 2012

Stroke

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Background and Purpose-Prior use of antiplatelet agents improves stroke outcome in patients undergoing thrombolytic therapy as shown by reduced arterial reocclusion, although the risk of cerebral hemorrhage can be increased. Methods-The effect of cilostazol, an antiplatelet drug that improves endothelial function through upregulation of intracellular cAMP, on cerebral hemorrhage after thrombolytic therapy was investigated using a highly reproducible transient ischemia model. Results-Treatment with cilostazol for 7 days before ischemia significantly suppressed the risk and severity of cerebral hemorrhage after injection of tissue-type plasminogen activator, although treatment with aspirin had no such protective effect compared with nontreated mice. Immunohistological analysis revealed that treatment with cilostazol suppressed disruption of the microvasculature in the ischemic area associated with reduced matrix metalloproteinase-9 activity. Conclusions-Our results suggest that patients treated with cilostazol before onset of stroke could have a lower risk of cerebral hemorrhage after thrombolytic therapy and might also have a longer therapeutic time window for thrombolysis. Furthermore, the risk of cerebral hemorrhage can be significantly altered by prestroke therapies, and analysis of the effects of multiple drugs on tissue-type plasminogen activator-induced cerebral hemorrhage in animal models is essential for the extending safe and effective thrombolytic therapy to a wider group of patients.

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Section: Kasahara Et Al Cilostazol and Tpa-induced Hemorrhage 503mentioning

confidence: 99%

Cilostazol Reduces the Risk of Hemorrhagic Infarction After Administration of Tissue-Type Plasminogen Activator in a Murine Stroke Model

Kasahara

Nakagomi

Matsuyama

et al. 2012

Stroke

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“…One recent study indicated that AMPK suppresses iNOS expression through the inhibition of NFB (Aoki et al, 2010). We, therefore, examined the possible effect of FFA on NFB.…”

Section: Downloaded Frommentioning

confidence: 99%

“…First, AMPK can be activated by Ca 2ϩ through the CaMKK␤ pathway (Stahmann et al, 2006). Second, similar to FFA, AMPK has both anti-inflammatory and channel-regulatory activity (Pilon et al, 2004;Carattino et al, 2005;Cheng et al, 2007;Mace et al, 2008;Jeong et al, 2009;Klein et al, 2009;Kongsuphol et al, 2009;Kréneisz et al, 2009;Aoki et al, 2010;Cai et al, 2010;Shin et al, 2010). For example, both FFA and AMPK have been reported to suppress the inflammatory mediator-induced expression of inducible nitric-oxide synthase (iNOS) (Paik et al, 2000;Aoki et al, 2010) and inhibit sodium channel (Carattino et al, 2005;Yau et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…pathways and switches on ATP-producing pathways. In addition to its regulatory functions on cellular metabolic pathways, AMPK has anti-inflammatory effects (Pilon et al, 2004;Cheng et al, 2007;Jeong et al, 2009;Aoki et al, 2010;Cai et al, 2010;Shin et al, 2010). In addition, it promotes angiogenesis, protects cells from apoptosis (Shaw et al, 2004), and modulates a variety of channel activities (Carattino et al, 2005;Mace et al, 2008;Klein et al, 2009;Kongsuphol et al, 2009;Kréneisz et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Nonsteroidal Anti-Inflammatory Drug Flufenamic Acid Is a Potent Activator of AMP-Activated Protein Kinase

Chi

Li²,

Yan³

et al. 2011

J Pharmacol Exp Ther

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Flufenamic acid (FFA) is a nonsteroidal anti-inflammatory drug (NSAID). It has anti-inflammatory and antipyretic properties. In addition, it modulates multiple channel activities. The mechanisms underlying the pharmacological actions of FFA are presently unclear. Given that AMP-activated protein kinase (AMPK) has both anti-inflammatory and channel-regulating functions, we examined whether FFA induces AMPK activation. 1) Exposure of several different types of cells to FFA resulted in an elevation of AMPK␣ phosphorylation at Thr172. This effect of FFA was reproduced by functionally and structurally similar mefenamic acid, tolfenamic acid, niflumic acid, and meclofenamic acid. 2) FFA-induced activation of AMPK was largely abolished by the treatment of cells with 1,2-bis(2-aminophenoxy)ethane-N,N,NЈ,NЈ-tetraacetic acid tetrakis(acetoxymethyl ester) (an intracellular Ca 2ϩ chelator) or depletion of extracellular Ca 2ϩ , whereas it was mimicked by stimulation of cells with the Ca

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“…Thus, cilostazol seems to be non-inferior, and might be superior, to aspirin for stroke prevention after an ischemic stroke. Potential beneficial effects of cilostazol include suppression of atherosclerosis 6,7) , inhibition of inflammatory mediators [8][9][10] , and promotion of reverse cholesterol transport 11) . Endothelial progenitor cells (EPCs) play a key role in the maintenance and repair of vascular integrity in response to endothelial injury 12,13) .…”

mentioning

confidence: 99%

Comparison of the Effect of Cilostazol with Aspirin on Circulating Endothelial Progenitor Cells and Small-Dense LDL Cholesterol in Diabetic Patients with Cerebral Ischemia: A Randomized Controlled Pilot Trial

Ueno

Koyama

Mima

et al. 2011

JAT

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Aim:A recent clinical trial showed the preventive effect of cilostazol on cerebrovascular diseases. We compared the effects of cilostazol with aspirin on circulating endothelial progenitor cells (EPCs), a surrogate marker for cardiovascular disease, and lipid metabolism in a randomized controlled trial (UMIN000000537). Methods: Forty-nine diabetic outpatients with leukoaraiosis or asymptomatic old cerebral infarction were enrolled in the study with written informed consent. They were randomly assigned to a cilostazol (200 mg daily, n 24) or aspirin group (100 mg daily, n 25), and followed for 16 weeks. Changes in circulating CD34 CD45 low CD133 VEGFR2 EPCs ( EPC) were a primary endpoint. Changes in CD34 CD45 low CD133 progenitor cells ( PC), p-selectin-positive platelet, plateletmonocyte binding measured by flow cytometry, LDL-, HDL-, small dense LDL (sdLDL)-cholesterol and triacylglycerol were the secondary endpoints. Results: Twenty patients in each group completed the study. EPC were significantly higher in the cilostazol group than aspirin group at 16 weeks, while PC were already significantly higher at 4 weeks in the cilostazol group. Changes in p-selectin-positive platelets and platelet-monocyte binding were similar in both groups. The cilostazol group showed significantly less sdLDL-and higher HDLcholesterol than the aspirin group at both 4 and 16 weeks. EPC were significantly and inversely correlated with changes of sdLDL, while positively with those of HDL. Analysis of covariance showed that a significant relation of EPCs with cilostazol treatment was confounded by changes in HDL-and sdLDL-cholesterol. Conclusion: Cilostazol increases circulating EPCs and decreases small-dense LDL in diabetic patients with cerebral ischemia. J Atheroscler Thromb, 2011; 18:883-890.

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Anti-Inflammatory Role of Cilostazol in Vascular Smooth Muscle Cells In vitro and In vivo

Cited by 48 publications

References 14 publications

Cilostazol Reduces the Risk of Hemorrhagic Infarction After Administration of Tissue-Type Plasminogen Activator in a Murine Stroke Model

Cilostazol Reduces the Risk of Hemorrhagic Infarction After Administration of Tissue-Type Plasminogen Activator in a Murine Stroke Model

Nonsteroidal Anti-Inflammatory Drug Flufenamic Acid Is a Potent Activator of AMP-Activated Protein Kinase

Comparison of the Effect of Cilostazol with Aspirin on Circulating Endothelial Progenitor Cells and Small-Dense LDL Cholesterol in Diabetic Patients with Cerebral Ischemia: A Randomized Controlled Pilot Trial

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