At present, brachial-ankle pulse wave velocity (baPWV) can be measured easily and noninvasively. We studied the correlation between aortic damage estimated by baPWV and that determined by measuring the length of abdominal aortic calcification (AAC) on X-ray films, which parameter has been significantly associated with cardiovascular morbidity and mortality. baPWV was measured using the form PWV/ankle brachial index (ABI) device in 97 patients free of end-stage renal failure or peripheral arterial disease. baPWV corre- cance has not been fully investigated. Therefore, the present study was designed to evaluate the efficacy of baPWV in identifying vascular damage. For this purpose, we measured the length of abdominal aortic calcification (AAC) on X-ray films, which has been reported to correlate significantly with cardiovascular morbidity and mortality (7,8), and correlated this parameter, as well as other clinical and laboratory parameters, with baPWV.

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Tissue factor (TF) protein was overexpressed by macrophages and smooth muscle cells (SMCs) and deposited in the extracellular matrix of atherosclerotic intimas, probably resulting in enhanced procoagulant activity and the intimate participation in either thrombus formation or intimal fibrin deposition after the exposure of flowing blood and permeated fibrinogen to TF in atherosclerotic lesions. On the other hand, APO(a) was localized both in the stroma and within some macrophages. Fibrin deposition, which was more frequently detected in the matrix of advanced lesions than in that of early lesions, occasionally colocated with cell- and matrix-associated TF and APO(a) deposited in the matrix. These findings further support the hypothesis that the coagulation and fibrinolysis systems can play an essential role in the initiation and progression of atherosclerosis through fibrin deposition both in atherosclerotic plaques and on the arterial surface by neointimal hypercoagulability and a hypofibrinolytic state, which can also participate in SMC proliferation due to the decreased activation of TGF-beta by embedded and deposited APO(a). The clinical implications of these phenomena may thus contribute to future investigations in the prevention and treatment of atherosclerotic diseases.

The present study was designed to develop an animal model of multiple risk factors, including obesity, hypertension, non-insulin-dependent diabetes mellitus, and hyperlipidemia. Hypothalamic obesity was induced by neonatal monosodium glutamate (MSG) treatment in spontaneously hypertensive rats (SHR). Female newborn SHR were treated intraperitoneally with 2 or 4 mg/kg body weight of MSG for 5 days. Obesity developed in SHR treated with 4 mg/kg of MSG but not in SHR treated with 2 mg/kg of MSG. Obese SHR had impaired glucose tolerance, hyperinsulinemia, and hypertriglyceridemia. However, the severity of hypertension was attenuated in obese SHR as compared with control SHR. The degree of obesity was closely related to the metabolic abnormalities, but inversely correlated with the blood pressure level. Macrovascular changes were investigated in obese SHR at 14 months of age. Intimal thickening was accelerated in the carotid artery of obese SHR as compared with that of nonobese SHR. Aortic contents of DNA and total cholesterol were significantly increased in obese SHR. SHR associated with MSG-induced obesity showed major manifestations of metabolic syndrome X. This animal model may be useful to study the clustering of risk factors for the development of macrovascular diseases. (Hypertens Res 1998; 21: 1-6) Key Words: insulin resistance, diabetes mellitus, syndrome X, atherosclerosis, animal model Obesity, hypertension, non-insulin-dependent diabetes mellitus (NIDDM), and hyperlipidemia frequently exist in the same individual, and clustering of these closely related risk factors markedly increases the incidence and prevalence of atherosclerotic diseases (1-7). Insulin resistance and consequent hyperinsulinemia or visceral fat accumulation may play a pathogenetic role in the clustering of risk factors, i. e. , metabolic syndrome X. However, the relationship among these risk factors, especially that between hypertension and other metabolic diseases, is controversial (5-8). Our understanding of metabolic syndrome X may be enhanced by the development of an animal model of this syndrome. We therefore designed the present study to induce experimental obesity in spontaneously hypertensive rats (SHR) by treatment with small or large doses of monosodium glutamate (MSG). MSG induces hypothalamic damage when given during neonatally, leading to stunted growth and obesity (9). We studied the effects of MSG-induced obesity on hypertension, glycemia, lipidemia, and the development of macrovascular changes in the obese SHR. Materials and MethodsSHR were from our inbred colony and were bred in specific-pathogen-free conditions at Kyushu University Animal Center, where both temperature and lighting (on from 8:00 am to 8:00 pm) were controlled. They had free access to tap water and a standard chow diet, which contained 51.6% carbohydrate, 24.8% protein, 7.0% minerals, 4.4% fat, and 3.5% cellulose (flea Japan Inc., Tokyo, Japan). Animals were cared for as directed by guidelines of Kyushu University. Female newborn SHR were treated intrap...

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While non-enzymatic glycation of long-lived tissue proteins such as collagen has been implicated in chronic complications of diabetes mellitus, its role in the aetiology of diabetic macroangiopathy has not been elucidated. To test the hypothesis that glycation of collagen abolishes the inhibitory effect of native collagen on the proliferation of human smooth muscle cells, we obtained smooth muscle cells from human gastric arteries and cultured them on dishes coated with glycated or non-glycated collagen. The proliferation of human smooth muscle cells in the presence of 10% fetal calf serum or platelet derived growth factor-BB (10 ng/ml) was inhibited by type 1 collagen coated on the dishes. Glycation of collagen with glucose 6-phosphate for 7 days abolished the growth-inhibitory effect of native collagen. Succinylation of collagen, which like glycation blocked the lysyl residues in collagen, also abolished the growth-inhibitory effect. Adhesion of human smooth muscle cells to collagen-coated dishes was not affected by glycation of collagen. Addition of glycated albumin to the medium did not affect the growth of human smooth muscle cells on plastic dishes. The inhibition of human smooth muscle cell proliferation by collagen was not reversed by the glycation of collagen in the presence of aminoguanidine. Results suggest that early glycation abolishes the inhibitory effect of collagen on human smooth muscle cell proliferation and may thus participate in the progression of macro-angiopathy in diabetes.

, Kenzo IINO, Noriyasu SHINOHARA, and Masatoshi FUJISHIMAWe compared the effects of hypothalamic obesity induced by neonatal monosodium glutamate (MSG) treatment between spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY).Newborn WKY and SHR were injected intraperitoneally with 4 mg/kg body weight of MSG daily for 5 days.At 6 months of age, the obesity of SHR was more advanced than that of WKY, but at 14 months of age the severity of obesity was similar between the two strains. Hypertriglyceridemia was enhanced in MSG-treated SHR as compared with MSG-treated WKY. Systolic blood pressure measured by the tail-cuff method was consistently lower in MSG-treated SHR than in control SHR, whereas blood pressure was not affected by neonatal MSG treatment in WKY. Food restriction reduced body weight more in control SHR than in control WKY, with the former also showing enhanced ketogenesis. Neonatal MSG treatment abolished the accelerated reduction of body weight in SHR. Serum leptin concentration was markedly increased in MSGtreated obese rats, though no differences were seen between WKY and SHR in the control or MSG-treated groups. Serum leptin was closely correlated with both Lee obese index and mesenteric fat weight over the strain. Blood flow in interscapular brown adipose tissue (BAT) measured by Laser Doppler flowmetry was significantly increased in response to i 3-adrenoceptor agonist BRL26830A in both the control and MSGtreated rats. However, the response of blood flow was not affected by MSG treatment or strain difference.The present study demonstrated some strain differences in response to neonatal MSG treatment between WKY and SHR. These differences could not be explained by the difference in serum leptin level or N3-adrenergic reactivity in BAT. (Hypertens Res 2000; 23: 503-510)