Probucol and ticlopidine: effect on platelet and monocyte activation markers in hyperlipidemic patients with and without type 2 diabetes

Nomura, Shosaku; Takahashi, Nobuyuki; Inami, Norihito; Kajiura, Takayuki; Yamada, K; Nakamori, Hisato; Tsuda, Nobuyuki

doi:10.1016/j.atherosclerosis.2004.01.027

Cited by 54 publications

(39 citation statements)

References 51 publications

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“…PDMP were detected using a modification of the previously reported method. [4][5][6][7] An aliquot (10 ml) of platelet suspension (3 Â 10 8 /ml) was added to 100 ml of 2-[4-(2-hydroxyethyl)-1-piperazinyl] ethanesulphonic acid (HEPES)-Tyrode's buffer containing 5 mmol/l ethylene glycol-bis-(2-aminoethyl ether)-N,N,N 0 ,N 0 -tetraacetic acid (EGTA), and both intact and aggregated platelets were removed by centrifugation at 1000 g for 15 min to obtain a supernatant that only contained microparticles. Then washed intact platelets (10 ml, 3 Â 10 8 /ml) were added to the supernatant, and incubation with KMP-9 (a fluorescein isothiocyanate (FITC)-labelled monoclonal antibody for platelet glycoprotein (GP) IX was performed for 30 min in the dark at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…3,4 PDMP have procoagulant activity, and some studies have assessed the potential role of PDMP in diabetic complications. [4][5][6][7][8] Monocytes also can synthesize procoagulants, which are largely tissue factors, 9,10 and monocyte vesiculation is a possible mechanism for the dissemination of membrane-associated procoagulant activity. 11 We previously reported that a high level of monocyte-derived microparticles (MDMP) may be a marker of vasculopathy in diabetic patients.…”

Section: Introductionmentioning

confidence: 99%

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Effect of nifedipine on adiponectin in hypertensive patients with type 2 diabetes mellitus

et al. 2006

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Nifedipine, a dihydropyridine calcium antagonist, improves endothelial function in patients with hypercholesterolaemia by enhancing nitric oxide (NO) activity, and increases endothelial NO bioavailability by antioxidant mechanisms. We administered a long-acting nifedipine formulation (controlled release (CR) nifedipine: 20 mg/day) to hypertensive patients for 6 months. There were no other changes of drug treatment during therapy with CR nifedipine. Clinical and biochemical data obtained before and after CR nifedipine administration were compared. All markers were measured by enzyme-linked immunosorbant assay. The levels of soluble markers (soluble CD40 ligand, soluble P-selectin, and soluble E-selectin), microparticles (MP) (platelet-derived MP, monocyte-derived MP, and endothelial cell-derived MP), and adiponectin differed between the control group and the hypertension group. The levels of these markers were also different in hypertensive patients with and without type 2 diabetes compared with the control group. In the hypertensive patients with type 2 diabetes, all markers except adiponectin decreased significantly after 3 months of CR nifedipine treatment. In contrast, markers were unchanged in the hypertensive patients without type 2 diabetes. Adiponectin was increased after 6 months of CR nifedipine treatment in hypertensive patients with type 2 diabetes. The effects of CR nifedipine on platelet/monocyte activation and adiponectin levels demonstrated in the present study indicate the potential effectiveness of calcium antagonist therapy for hypertensive patients with type 2 diabetes.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of nifedipine on adiponectin in hypertensive patients with type 2 diabetes mellitus

et al. 2006

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“…20,21 We evaluated in vivo effects of LMWF on blood pressure and local blood flow, ex vivo effects on endothelium-dependent vasodilation and eNOS expression, and in vitro effects of LMWF on eNOS phosphorylation in endothelial cells, and compared them with the effects of probucol, a lipidmodifying drug with powerful antioxidant and antiinflammatory properties used for prevention of type 2 diabetes mellitus. [22][23][24] We found that LMWF profoundly protects endothelial function against the complications of diabetes.…”

mentioning

confidence: 89%

Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats

Cui

Zheng

Zhang

et al. 2014

Laboratory Investigation

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Endothelial dysfunction, characterized by impairment of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) bioavailability, has been implicated in diabetic cardiovascular pathogenesis. In this study, low-molecular-weight fucoidan (LMWF), which has multiple biological activities including anti-inflammatory and anti-oxidative properties, was investigated for its protective effect against endothelial dysfunction in Goto-Kakizaki type 2 diabetic rats. LMWF (50, 100, or 200 mg/kg/day) or probucol (100 mg/kg/day) were given to diabetic rats for 12 weeks. Basal blood pressure, acetylcholine-or flow-mediated relaxation of mesenteric and paw arteries, endothelium-dependent dilation of aorta, eNOS phosphorylation, and NO production were measured using laser Doppler flowmetry, force myograph, hematoxylin and eosin staining, western blot analysis, and an NO assay. We found that LMWF robustly ameliorated the basal hypertension and impairment of endothelium-dependent relaxation in the aorta, as well as mesenteric and paw arteries in diabetic rats. In addition, the reduction in eNOS phosphorylation at Ser1177, eNOS expression, and NO production because of diabetes were partially reversed by LMWF treatment. However, probucol, a lipid-modifying drug with antioxidant properties, displayed only mild effects. Moreover, LMWF induced, in a dose-dependent manner, endotheliumdependent vasodilation and eNOS phosphorylation at Ser1177 in normal aorta, and also promoted Ser1177 phosphorylation and NO synthesis in primary cultured vasoendothelial cells. Thus, these data demonstrate for the first time that fucoidan protects vasoendothelial function and reduces basal blood pressure in type 2 diabetes rats via, at least in part, preservation of eNOS function. Fucoidan is therefore a potential candidate drug for protection of endothelium in diabetic cardiovascular complications. KEYWORDS: diabetes; endothelium-dependent vasodilation; endothelial nitric oxide synthase; low-molecular-weight fucoidan; nitric oxide Diabetic patients are at high risk of endothelial dysfunction and vascular lesions, because of multiple harmful stimuli, such as hyperglycemia, hyperlipidemia, and oxidative stress. These patients are susceptible to atherosclerosis, hypertension, and peripheral vascular disease. 1,2 It is well established that endothelium-derived nitric oxide (NO) maintains vascular homeostasis and health through vasodilation and protection of vasculature from various damaging agents. [3][4][5] Loss of NO induces increased activity of proinflammatory transcription factors, such as nuclear factor kappa B, resulting in expression of leukocyte adhesion molecules and production of chemokines and cytokines, which further promote endothelial inflammation and atherosclerosis. 5,6 Therefore, the endothelial dysfunction caused by imbalance of NO bioavailability in early-stage diabetes has been implicated as a sign or a predictor of a future cardiovascular event. [6][7][8] Mechanistically, a disturbance in endothelial NO synthase (eNOS) activity, refe...

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“…Procoagulant platelet-derived MVs [47,48] , monocytederived MVs [14] , and endothelial-derived MVs [49] are significantly increased in patients with diabetes, even in wellcontrolled DM without complications [50] and newly diagnosed T2DM [51] . In addition, patients with diabetes accompanied by hyperten sion [15,16,32,[52][53][54][55][56][57] , hyperlipidemia [58][59][60] , stable coronary disease [61] , angina with [62] or without [17] symptomatic episodes, myocardial infarction [49,63] , diabetic retinopathy, and nephropathy [33,64] have significantly increased levels of procoagulant MVs compared with those without diabetic complications. Therefore, elevated levels of MVs may be associated with the increased risk of thrombo-embolic diabetic complications.…”

Section: Mvs and Thrombosismentioning

confidence: 99%

“…An in vivo study showed that artificially induced high levels of insulin can cause increased monocyte TF expression in healthy volunteers [68] , suggesting the pro-thrombotic effect of hyperinsulinemia. Administration of antiplatelet drugs can significantly decrease circulating MVs and activated platelets in patients with diabetes [47,59,[69][70][71][72] .…”

Section: Mvs and Thrombosismentioning

confidence: 99%

Microvesicles and diabetic complications — novel mediators, potential biomarkers and therapeutic targets

2014

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Probucol and ticlopidine: effect on platelet and monocyte activation markers in hyperlipidemic patients with and without type 2 diabetes

Cited by 54 publications

References 51 publications

Effect of nifedipine on adiponectin in hypertensive patients with type 2 diabetes mellitus

Effect of nifedipine on adiponectin in hypertensive patients with type 2 diabetes mellitus

Low-molecular-weight fucoidan protects endothelial function and ameliorates basal hypertension in diabetic Goto-Kakizaki rats

Microvesicles and diabetic complications — novel mediators, potential biomarkers and therapeutic targets

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