There is a close inter-relationship between oxidative stress, coagulation, inflammation, and smooth muscle cell growth as key components of atherosclerosis (Fig. 1). As an analgesic and anti-pyretic, aspirin has been in use for over a century. It acetylates the COX enzyme, irreversibly inhibiting the formation of prostaglandin. Its action on platelet TxA₂ has highlighted its role as an anti-thrombotic agent in cardiovascular patients. Over the last two decades, unique anti-inflammatory properties of aspirin not shared by other non-steroidals have been discovered. Aspirin biotransforms into salicylate, which has diverse but potent anti-inflammatory properties. As we strive to better understand the concepts of atherogenesis, chronic inflammation, oxidative stress, and endothelial activation, these novel effects of aspirin provide new insights as to how this wonder drug works. These effects of aspirin alter many, if not all, components of the atherogenesis cascade shown in Fig. 1.

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As a risk factor for cardiovascular and cerebrovascular disease, hypertension and hyperlipidemia are believed to provoke vascular damage leading to a hypercoagulative state. The aim of the present study was to investigate the coagulative and fibrinolytic activity and hepatic mRNA expression of the coagulative factors in spontaneously hypertensive and hyperlipidemic female rats (SHHR: > 150 mmHg of systolic blood pressure, > 150 mg/dl of plasma cholesterol). Plasma levels of fibrinogen, thrombin-antithrombin III (ATIII) complexes and ATIII in the SHHR at 9 months of age increased significantly compared with those of age-matched Sprague-Dawley rats (SD). In the SHHR, the hepatic mRNA expression of the α- and β-chains, but not the γ-chain of fibrinogen and prothrombin was significantly enhanced. Therefore, the hyperfibrinogenemia in the SHHR was demonstrated to be due to the increase in hepatic mRNA expression of α- and β-chains of fibrinogen. The pathological findings of the aortic arch from the 9-month old SHHR were cytoplasmic vacuolization and intimal thickening in the endothelium. These results suggest that hypercoagulation concomitant with the increase in hepatic mRNA expression of fibrinogen components may contribute to the development of atherosclerosis in the SHHR.

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This study investigated whether smoking habits had a differential influence on waist circumference and obesity-related disorders in nonobese and obese men. We investigated 359 men with smoking habits confirmed by their spouses, including 172 nonobese men (BMI < 25) and 187 obese men (BMI ≥ 25). There were 113 nonobese smokers and 129 obese smokers. Obesity-related disorders were defined as hypertension, dyslipidemia, hyperglycemia, hyperuricemia, or treatment for one or more of these disorders. Nonobese subjects showed no differences of age, BMI, and waist circumference between smokers and nonsmokers, but smokers had a higher incidence of obesity-related disorders. Obese smokers were younger than obese nonsmokers and had a larger waist circumference, but a similar prevalence of obesity-related disorders. The prevalence of obesity-related disorders was similar between obese nonsmokers and smokers, but the smokers were younger. In nonobese subjects, smoking may increase obesity-related disorders by a mechanism other than visceral fat accumulation. In obese subjects, however, smoking may promote visceral fat accumulation. Further investigations will be necessary to better elucidate the relationship between the promotion of visceral fat accumulation in obese subjects by smoking and obesity-related disorders.

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Objective: A statin, a potent lipid-lowering drug, improves pain-free walking distance in patients with peripheral arterial disease (PAD) without increasing the ankle-brachial pressure index (ABI). Arterial stiffness affects the blood flow of peripheral arteries. The purpose of this study was to evaluate the effect of cholesterol-lowering with atorvastatin on regional arterial stiffness in patients with type 2 diabetes mellitus.
Methods: The subjects were 22 type 2 diabetic patients with hypercholesterolemia, who received atorvastatin at a daily dose of 10 mg for 6 months. Before and after the treatment with atorvastatin, we measured pulse wave velocity (PWV) in the heart-brachial, heart-carotid, heart-femoral and femoral-ankle segments.
Results: Following treatment with atorvastatin, femoral-ankle PWV showed a significant reduction. The PWV of other arterial segments tended to decrease, although the changes were not statistically significant. We found no significant changes in blood pressure, heart rate, ABI, or plasma concentrations of glucose, L-arginine and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial function.
Conclusions: Atorvastatin treatment was associated with an improvement in the stiffness of leg arteries in type 2 diabetes mellitus. This may partly explain the statin-mediated improvement of walking performance in those with PAD.

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Fibrates are commonly used lipid-lowering agents that act via PPARα, a member of the nuclear hormone receptor superfamily. The mechanism(s) of fibrate-induced changes in the hepatic canalicular membrane and bile lipids are still unknown. Therefore, the aim of this study was to investigate the influence of fibrates on hepatic lipid metabolism and to assess the hepatocellular cytoprotective effect on hepatocyte canalicular membrane. Male ICR mice were fed standard chow with or without bezafibrate (100 mg/kg) for 6 days. The expression of canalicular membrane transporters (Mdr2 and Mrp2) was evaluated by RT-PCR and Western blotting. Canalicular membrane fluidity was also investigated. Canalicular membrane fluidity was markedly increased by fibrates. The expression of mdr 2 and mrp2 mRNA and protein showed a significant increase in fibrate-treated mice. These results suggested that fibrates improve liver function by enhancing bile secretion. The mechanism of the choleretic action of fibrate therapy might involve the enhancement of bile acid-independent bile secretion, since increased expression of Mdr2 and Mrp2 was found in fibrate-treated animals. These changes were very likely mediated by PPARα, and the increase of canalicular membrane fluidity may have been partly associated with enhancement of this transporter activity.

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This study was conducted to clarify the characteristics of colestimide responders. Forty-seven non-diabetic patients with high levels of low-density lipoprotein cholesterol (LDL-C) received colestimide at 3,000 mg/day and were followed up for 4 months. After 4 months, body weight was reduced but the change was not statistically significant. Total serum cholesterol (TC) and LDL-C levels significantly decreased from 280 to 232 mg/dl and from 195 to 150 mg/dl, respectively (p < 0.01 versus before colestimide was administered). Serum triglyceride (TG) levels increased, but the change was not significant. Preheparin lipoprotein lipase mass (preheparin LPL mass) at baseline was significantly higher in colestimide responders (greater than a 20% decrease of LDL-C: n = 28) than non-responders (76.2 ng/ml versus 50.3 ng/ml, p < 0.05: n = 19). Next, the subjects were divided into those with a high (n = 33) and low (n = 14) preheparin LPL mass at baseline. LDL-C levels were significantly decreased in patients with a high preheparin LPL mass while TG levels were significantly increased in patients with a low preheparin LPL mass. These results suggest that baseline preheparin LPL mass may be a marker of the response to colestimide.

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To investigate the relationship between the blood pressure control level and cardiovascular risk in type 2 diabetic patients, we evaluated home blood pressure, office blood pressure, biochemical data, and carotid echographic and echocardiographic findings in 148 patients with type 2 diabetes. According to the criteria for hypertension in the guidelines of the Japanese Society of Hypertension, we classified patients into a normotensive group with home systolic blood pressure in the morning (morning HSBP) < 135 mmHg and office systolic blood pressure (OSBP) < 140 mmHg, an office hypertension group with a morning HSBP < 135 mmHg and OSBP ≥ 140 mmHg, an isolated home hypertension in the morning group with morning HSBP ≥ 135 mmHg and OSBP < 140 mmHg, and a sustained hypertension group with morning HSBP ≥ 135 mmHg and OSBP ≥ 140 mmHg. In the isolated home hypertension in the morning group, the fasting insulin level, urinary albumin excretion, maximum carotid artery intima-media complex thickness, and left ventricular posterior wall thickness were significantly higher and the coefficient of variation for RR intervals was significantly lower than in the normotensive group. These results suggest that isolated home hypertension in the morning is a risk factor for target organ damage in type 2 diabetic patients.

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In the article “Pitavastatin Enhanced Lipoprotein Lipase Expression in 3T3-L1 Preadupocytes” by Saiki A, et al., which appeared in JAT 2005, 12: 163.168, Figure (No.3, No.4, No.5, No.6) are incorrect. The editiorial staff apologizes to the authors and all readres. The correct Figure (No.3, No.4, No.5, No.6) are presented with corresponding below. Wrong:Figure (No.3, No.4, No.5, No.6) are incorrect.
Right:The correct Figure (No.3, No.4, No.5, No.6) are presented with corresponding below.

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