The constellation of metabolic abnormalities including centrally distributed obesity, decreased high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, elevated blood pressure (BP), and hyperglycaemia is known as the metabolic syndrome. Associated with a 3 fold and 2 fold increase in type 2 diabetes and cardiovascular disease (CVD), respectively, it is thought to be a driver of the modern day epidemics of diabetes and CVD and has become a major public health challenge around the world.
Since its initial description, several definitions of the syndrome have emerged. Each of these definitions used differing sets of criteria, which reflected contrasting views on pathogenic mechanisms and the need for clinical usefulness. The use of these definitions to conduct research into the metabolic syndrome in diverse populations resulted in wide ranging prevalence rates, inconsistencies and confusion, and spurred on the vigorous debate regarding how the metabolic syndrome should be defined. In response to this controversy, the International Diabetes Federation (IDF) has recently proposed a new definition, which is applicable to populations around the world. It is envisaged that the development of the new definition for the metabolic syndrome will help resolve the confusion caused by the number of earlier attempts to define this important entity.

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Despite reports that statin treatment reduces the rate of coronary restenosis with a balloon expandable stent, there is no evidence that statins affect the incidence of restenosis with a self-expanding Radius stent. Ninety-five patients with acute coronary syndrome who had been implanted with a Radius stent were classified into two groups: those with hyperlipidemia and initial statin treatment (statin group, n = 38) and those without statin treatment (comparative group, n = 57). At six months after stent implantation, the rate of coronary restenosis was significantly lower in the statin group (10.5%) than control group (28.1%) (p = 0.033), while there were no differences in morphology, maximal inflation presure or stent size between the two groups. Interestingly, there was no difference in the serum lipid profile between the two groups at the 6-month follow-up, although the statin group had a significantly lower rate of restenosis. In conclusion, initial statin therapy reduced the rate of coronary restenosis even when a Radius stent was implanted.

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We investigated the effect of 7-ketocholesterol (7-KCHO) on the activity of matrix metalloproteinase (MMP-9) in human monocytic THP-1 cells, and the inhibition of this effect by fluvastatin. In cells incubated with 7-KCHO or cholesterol, the activity of MMP-9 was enhanced, accompanying an increase in the secretion of MMP-9 proenzyme (pro-MMP-9). However, the activity of MMP-9 and the amount of pro-MMP-9 were significantly greater following incubation with 7-KCHO than cholesterol. Neither 7-KCHO nor cholesterol influenced the amount of tissue inhibitor of metalloproteinase (TIMP)-1 secreted by THP-1 cells. When fluvastatin was added to the cells, the MMP-9 activity stimulated by 7-KCHO or cholesterol decreased significantly, accompanying a decrease in the secretion of pro-MMP-9 and TIMP-1. The inhibition of pro-MMP-9 secretion by fluvastatin was stronger in the cells incubated with 7-KCHO than with cholesterol. These results suggest that 7-KCHO activates macrophage and enhances MMP-9 activity, and its effects may be inhibited by fluvastatin.

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Objectives: We tried to elucidate angiographical predictors of no-reflow and to determine a preferable recanalization therapy based on the morphology of lesions. Methods: Seventy-six patients were randomly assigned into groups to receive primary angioplasty (n = 41) or intracoronary thrombolysis (n = 35). Based on angiography, occlusive infarct-related lesions were divided into thrombus-rich and hard plaque lesions. The outcome of the two therapies used for each lesion was compared. Results: The incidence of no-reflow was higher in the thrombus-rich than hard plaque lesions (38 percent vs. 0 percent, p = 0.006); the left ventricular ejection fraction in the chronic phase was lower (46 ± 6 percent vs. 55 ± 5 percent, p < 0.001) for primary angioplasty than thrombolysis. No-reflow was not observed in the hard plaque lesions. However, the incidence of additional reperfusion therapy (88 percent vs. 8 percent, p < 0.001) was higher in the patients who underwent thrombolysis rather than primary angioplasty. Conclusions: We suggest that thrombus-rich lesions in primary angioplasty may predict no-reflow in acute myocardial infarction, and thrombolysis prior to angioplasty may be preferable for these lesions. We also suggest that primary angioplasty may be more effective than thrombolysis for hard plaque lesions.

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To evaluate the effect of pravastatin on both lipid and glucose metabolism, twenty-two consecutive dyslipidemic patients treated with pravastatin at 10 mg/day for one year were enrolled in this study. The meal test, which consisted of 115 g of cookies (energy 560 kcal; glucose 75 g; protein 7 g; fat 24 g), was conducted before and after one year of treatment. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR), by the area under the IRI curve (AUC-IRI), and by the formula AUC-IRI × AUC-PG. After one year of treatment with pravastatin, the plasma glucose (PG), immunoreactive insulin (IRI) and C-peptide levels were unchanged after fasting and at 120 minutes after the meal test; however, PG, IRI and C-peptide levels at 60 minutes after the meal were all significantly decreased from baseline (p < 0.05). AUC-IRI and AUC-IRI × AUC-PG were also significantly decreased (p < 0.05). HOMA-IR was reduced by 26.8%, but the reduction was not significant. The triglyceride (TG) level was decreased after fasting and increased at 60 and 120 minutes after the meal test, but not significantly. This study demonstrated that pravastatin not only reduced serum lipids, but also improved the glucose metabolism, including insulin resistance, of dyslipidemic patients.

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In mammals, a fully developed, highly branched vascular system specialized for each particular organ or tissue is essential for obtaining metabolic nutrients supply. The formation of a blood-brain barrier that protects against environmental insults is a distinguishing feature of the brain’s vascular system. Since this is accomplished by cerebral endothelial cells (CECs), we analyzed the genes specifically and/or dominantly expressed in rat CECs using Suppression Subtractive Hybridization (SSH). We found 39 genes specifically and/or dominantly expressed in CECs. 24 genes of known function (thrombospondin-2, vimentin, etc.), 13 genes of known sequence but unknown function including 7 of ESTs (SNERG1, rat GPCR, etc.), and 2 novel genes. The physiological significance of these genes in CECs has been under investigation. SSH is useful for identifying genes regulated in an organ-specific manner in cells such as CECs to obtain clarification of their physiological roles.

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To determine the status of lipid management in patients with coronary artery disease (CAD) in Japan, we assessed CAD patients who had been receiving lipid-lowering therapy for six months in a cross-sectional survey conducted between June 2001 and December 2002. We defined the achievement rate as the percentage of patients who achieved the target LDL-C level (< 100 mg/dl) specified by the Japan Atherosclerosis Society (JAS). A total of 1,836 Japanese CAD patients were enrolled. In total, 549 (29.9%) achieved the target level. The achievement rate among those receiving statin therapy was 41.3%, which was significantly higher than that (23.4%) among the patients not receiving statin (P < 0.0001). The rate differed with the type of statin; being 54.7% for atorvastatin, 24.8% for pravastatin, 37.1% for simvastatin, and 27.8% for fluvastatin. A multiple regression analysis revealed that atorvastatin use (P < 0.001), and simvastatin use (P = 0.004) significantly contributed to the achievement of the target LDL-C level. In conclusion, large proportions of CAD patients are not achieving the JAS target and the success rates are not similar among different statin therapies, suggesting that cardiologists should consider a more aggressive lipid-lowering therapy with the appropriate choice of statins in Japanese CAD patients.

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Recent evidence suggests important roles for platelet activation in the progression of atherosclerosis. We have recently shown that P-selectin expression or the presence of platelet-monocyte aggregates, a well-characterized marker of platelet activation, is associated with carotid atherosclerosis in the general population. It is not clear, however, whether platelet activation is also associated with carotid atherosclerosis in patients with type 2 diabetes. In the present study, we measured circulating levels of platelet-monocyte aggregates in 120 patients with type 2 diabetes and 120 age- and gender-matched non-diabetic subjects, and examined their association with carotid atherosclerosis determined by arterial ultrasound. The percentage of platelet-monocyte aggregates was analyzed by CD41-positivity determined by whole-blood flow cytometry. Diabetic subjects (7.73 ± 4.04%, mean ± SD) showed significantly higher percentages of platelet-monocyte aggregates than non-diabetic subjects (6.03 ± 4.38%). The percentage of these aggregates was significantly and positively correlated with HbA_1c in both diabetic and non-diabetic subjects, with the association independent of other clinical factors. Logistic multiple regression analyses revealed that platelet-monocyte aggregates were significantly associated with the presence of carotid plaques independent of the status of glycemic control in diabetic subjects. Thus, an increase in platelet-monocyte aggregation in type 2 diabetic patients appears to be involved in the pathophysiology of carotid atherosclerosis.

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