Cilostazol, a potent phosphodiesterase type III inhibitor, selectively increases antiatherogenic high-density lipoprotein subclass LpA-I and improves postprandial lipemia in patients with type 2 diabetes mellitus

Ikewaki, Katsunori; Mochizuki, Kazuki; Iwasaki, Masafumi; Nishide, Ryoichi; Mochizuki, Seibu; Tada, Norio

doi:10.1053/meta.2002.35191

Cited by 32 publications

(15 citation statements)

References 44 publications

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“…First, it may be a secondary effect of improvement of risk factors for atherosclerosis. As also was found in several previous studies, [13][14][15] cilostazol treatment significantly decreased serum triglyceride and LDL cholesterol levels and significantly increased Values are meanϮSD. Comparisons of IMTs during treatment with baseline values were performed by paired t test.…”

Section: Discussionsupporting

confidence: 86%

The Phosphodiesterase Inhibitor Cilostazol Induces Regression of Carotid Atherosclerosis in Subjects With Type 2 Diabetes Mellitus

et al. 2010

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Background-Antiplatelet drugs are effective in preventing recurrence of atherosclerosis in type 2 diabetic patients.However, the efficacy and usefulness of 2 different antiplatelet drugs, aspirin and cilostazol, in the progression of carotid intima-media thickening are unknown. 001).In a regression analysis adjusted for possible confounding factors such as lipid levels and hemoglobin A 1c , the improvements in common carotid artery intima-media thickness with cilostazol treatment over aspirin treatment remained significant. Conclusions-Compared with aspirin, cilostazol potently inhibited progression of carotid intima-media thickness, an established surrogate marker of cardiovascular events, in patients with type 2 diabetes mellitus. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: C000000215.

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Section: Discussionsupporting

confidence: 86%

The Phosphodiesterase Inhibitor Cilostazol Induces Regression of Carotid Atherosclerosis in Subjects With Type 2 Diabetes Mellitus

et al. 2010

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“…[23][24][25] In type 2 DM patients, cilostazol improves the post-prandial lipemia. 26 Nomura et al demonstrated decreases in the plasma concentrations of soluble adhesion molecules and platelet-derived microparticles in patients with non-insulin dependent DM after oral administration of 150 mg/day of cilostazol for 4 weeks. 27 However, they did not measure pro-inflammatory markers or the ABI in their evaluation of the effect of cilostazol.…”

Section: Discussionmentioning

confidence: 99%

Effect of Cilostazol Treatment on Adiponectin and Soluble CD40 Ligand Levels in Diabetic Patients With Peripheral Arterial Occlusion Disease

Hsieh

Wang

2009

Circ J

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Circ J 2009; 73: 948 -954 eripheral arterial occlusion disease (PAOD) is a common manifestation of atherosclerosis in patients with type 2 diabetes mellitus (DM). 1,2 In Taiwan, approximately 33-50% of patients undergoing lower extremity amputation have DM, and more than 50% of them have PAOD. 3,4 The risk factors associated with PAOD are similar to those for coronary artery disease and cerebrovascular disease.It has been proved that atherosclerosis-related macroangiopathy is a result of chronic inflammation and endothelium dysfunction. Levels of high-sensitivity C-reactive protein (hs-CRP) and adiponectin have been found to be markers of chronic inflammation in many human studies. [5][6][7] Interaction of the multipotent immunomodulator CD40 ligand with its receptor is also as an important contributor to chronic inflammation and endothelium dysfunction. The soluble form of the CD40 ligand (sCD40L), a marker of proinflammatory and platelet activation, is high in the sera of DM patients with coronary artery disease. 8 However, few studies have investigated the relationships between PAOD and adiponectin and sCD40L levels.Cilostazol, a vasodilator and inhibitor of platelet aggregation, has been used in the treatment of chronic PAOD since 1988. Because little is known regarding its effects on PAOD and the aforementioned atherogenic cytokines in DM patients, we performed a randomized, placebo-controlled, single-blinded trial to examine the effect of cilostazol treatment on the serum levels of sCD-40L, adiponectin and hs-CRP in patients with type 2 DM. Methods SubjectsWe enrolled 92 PAOD patients (53 women, 39 men; mean age 63.3±18.8 years) and 100 non-PAOD patients as controls (58 women, 42 men; mean age 63.0±14.7 years) at our outpatient clinic from 2006 to 2008. Sex ratio and ranges of age and body mass index (BMI) were considered while selecting the controls. All patients were confirmed to have type 2 DM based on the 2005 American Diabetes Association diagnostic criteria and had received oral antidiabetic drugs (OADs) for more than 6 months. Because some antiplatelet, antihypertension and antihyperlipidemia drugs have an antiinflammatory effect, the dosages of all medications, including OADs, aspirin, antihypertension drugs and antihyperlipidemia drugs, were not changed for 6 months prior to the study or during the study period. We excluded any patient who had received insulin injections for more than 1 month or had been found to have had cardiogenic shock, unstable angina, old stroke, or myocardial infarction during the preceding 6 months, had an ankle systolic blood pressure (SBP) ≥200 mmHg, had been treated with insulin, and had impaired renal function (creatinine level >1.4 mg/dl), cancer, systemic inflammatory disease or (Received September 24, 2008; revised manuscript received November 26, 2008; accepted December 15, 2008; released online March 12, 2009 Effect of Cilostazol Treatment on Adiponectin and Soluble CD40 Ligand Levels in Diabetic Patients With Peripheral Arterial Occlusion DiseaseChing-Jung...

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“…In addition, weight loss, decreased levels of TC, TGs, and LDL, and increased levels of HDL were found in the mice in the combined treatment group relative to the mice in the HFD group (Table B). Cilostazol is known to increase HDL, and pravastatin also increases HDL in addition to lowering LDL in patients . Taken together, these results demonstrate that combination therapy with pravastatin and cilostazol could enhance the antiatherosclerotic effect of monotherapy with each drug, resulting in the modulation of serum cholesterol levels in LDLR mice.…”

Section: Discussionmentioning

confidence: 65%

Combination therapy with cilostazol and pravastatin improves antiatherogenic effects in low‐density lipoprotein receptor knockout mice

Park

Heo

2018

Cardiovascular Therapeutics

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Summary Aims Despite the therapeutic efficacy of statins and antiplatelet agents for atherosclerosis, monotherapy with each drug alone is often insufficient to achieve the patient's therapeutic goals. We previously showed that combined statin/antiplatelet agent/anti‐tumor necrosis factor (TNF) agent therapy (pravastatin/sarpogrelate/etanercept) reduces atherosclerotic lesions by inhibiting TNF, an atherogenic cytokine that contributes to the progression of arteriosclerosis. In addition, our previous study showed that combined treatment with pravastatin and cilostazol is effective for reducing TNF‐driven inflammation through anti‐TNF activity. Therefore, in the present study, we evaluated the additive effects of combined pravastatin and cilostazol therapy on atherosclerotic progression using low‐density lipoprotein receptor (LDLR) knockout (KO) mice. Methods Ten‐week‐old LDLR KO mice were fed a high‐fat, high‐cholesterol diet and orally administered pravastatin and cilostazol alone or in combination. Body weight, plasma lipid levels, and the levels of intracellular adhesion molecules and inflammatory cytokines were analyzed. In addition, aortas and aortic roots were stained with Oil Red O, and atherosclerotic plaques were quantified. Results The atherosclerotic plaques in the combined pravastatin and cilostazol treatment groups were significantly reduced compared to those in each drug monotherapy group. The combination therapy group also showed the downregulation of ICAM‐1, MOMA‐2, TNF, interleukin (IL)‐6, triglyceride, total cholesterol, and low‐density lipoprotein levels and the upregulation of high‐density lipoprotein levels compared to those of the pravastatin‐ or cilostazol‐treated groups. Conclusions Our results suggest that combination therapy with pravastatin and cilostazol exerts beneficial effects by decreasing atherosclerotic lesion progression and improving the pro‐inflammatory state in the vascular endothelium. These effects are mediated by the reduction in adhesion molecule expression, immune cell infiltration, and cytokine levels and the antiatherosclerotic modulation of serum cholesterol levels. Therefore, we conclude that combined treatment with pravastatin and cilostazol may be a more effective antiatherosclerotic strategy than treatment with either agent alone.

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Cilostazol, a potent phosphodiesterase type III inhibitor, selectively increases antiatherogenic high-density lipoprotein subclass LpA-I and improves postprandial lipemia in patients with type 2 diabetes mellitus

Cited by 32 publications

References 44 publications

The Phosphodiesterase Inhibitor Cilostazol Induces Regression of Carotid Atherosclerosis in Subjects With Type 2 Diabetes Mellitus

The Phosphodiesterase Inhibitor Cilostazol Induces Regression of Carotid Atherosclerosis in Subjects With Type 2 Diabetes Mellitus

Effect of Cilostazol Treatment on Adiponectin and Soluble CD40 Ligand Levels in Diabetic Patients With Peripheral Arterial Occlusion Disease

Combination therapy with cilostazol and pravastatin improves antiatherogenic effects in low‐density lipoprotein receptor knockout mice

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