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tiffness of large arteries has been related to cardiovascular mortality, but the mechanisms underlying this relationship have not been established. 1 Methods are used to estimate this stiffness include carotid ultrasound (CU) and pulse-wave-velocity (PWV). 2 Carotid artery stiffness detected by CU is known to representative of systemic arteriosclerosis. The measurement of PWV is very useful for diagnosing arteriosclerosis in any part of the body 3-7 and a new method for measuring PWV has been proposed in Japan. Brachial -ankle PWV (baPWV) measures the PWV in the arm and leg by applying air pressure using the volume plethysmographic method. However, baPWV is reportedly influenced by several factors such as blood pressure (BP), autonomic nerve function etc and therefore does not reflect arteriosclerosis in some cases.The stiffness parameter is reported to be independent of BP. 8 Beta of the thoracic descending aorta (TDA) has been obtained previously only by transesophageal echocardiography (TEE), 9 but recently this problem has been solved with the advent of the cardio-ankle vascular index (CAVI). CAVI is a new parameter that is also independent of BP 10-12 and in the present study, we examined the accuracy and usefulness of CAVI and compared it with other parameters of arteriosclerosis, using CU and serum lipids measurement in patients with chest pain syndrome. Methods Principle of CAVI and Method of MeasurementCAVI was obtained by substituting the stiffness parameter in the following equation for determining vascular elasticity and PWV. The stiffness parameter indicates BPindependent patient-specific vascular stiffness measured by arterial US. The stiffness parameter is calculated as: (1) where Ps and Pd are respectively the systolic and diastolic BP in mmHg. D is the diameter of the blood vessel and ∆D is the change of D.Bramwell-Hill's formula expresses the relationship between volume elastic modulus and PWV as follows:where ∆P is pulse pressure, is blood density, V is the volume of the blood vessel and ∆V is the change of V.From equation (2), the following formula is derived:where D is the diameter of the blood vessel and ∆D is the change of D. If we substitute equation (3) for equation (1), we obtain the stiffness parameter:CAVI is measured as follows. PWV is obtained by dividing vascular length (L) by the time (T) taken for the pulse wave to propagate from the aortic valve to the ankle Circ J 2007; 71: 1710 -1714 (Received February 15, 2007 revised manuscript received June 20, 2007; accepted July 4, 2007) Division of Cardiology, Tokuyama Central Hospital, Shunan, *Division Methods and ResultsThe purpose of this study was to evaluate the accuracy and usefulness of CAVI and to compare it with other parameters of arteriosclerosis by carotid ultrasound (CU). The instantaneous dimensional change of the TDA on TEE was measured simultaneously with systemic pressure of the brachial artery in 70 patients in sinus rhythm. There were significant correlations between CAVI and age (r=0.65, p<0.01), and CAVI and...

The crystal structure of recombinant murine interferon‐beta (IFN‐beta) has been solved by the multiple isomorphous replacement method and refined to an R‐factor of 20.5% against 2.6 A X‐ray diffraction data. The structure shows a variant of the alpha‐helix bundle with a new chain‐folding topology, which seems to represent a basic structural framework of all the IFN‐alpha and IFN‐beta molecules belonging to the type I family. Functionally important segments of the polypeptide chain, as implied through numerous gene manipulation studies carried out so far, are spatially clustered indicating the binding site(s) to the receptor(s). Comparison of the present structure with those of other alpha‐helical cytokine proteins, including porcine growth hormone, interleukin 2 and interferon gamma, indicated either a topological similarity in chain folding or a similar spatial arrangement of the alpha‐helices.

Toll-like receptor 4 (TLR4) and angiotensin II (AngII) induce vascular remodeling through the production of reactive oxygen species (ROS). AngII has also been shown to increase antioxidant enzyme extracellular superoxide dismutase (ecSOD). However, the roles of TLR4 in Ang II-induced ROS production, vascular remodeling and hypertension remain unknown. Mice lacking TLR4 function showed significant inhibition of vascular remodeling in response to chronic AngII infusion, with no impact on blood pressure. The increases in ROS level and NADPH oxidase activity in response to AngII infusion were markedly blunted in TLR4-deficient mice. Similar effects were observed in wild-type (WT) mice treated with a sub-depressor dose of the AT1 receptor antagonist irbesartan, which had no effects on TLR4-deficient mice. Intriguingly, the AngII infusion-induced increases in ecSOD activity and expression were rather enhanced in TLR4-deficient mice compared with WT mice, whereas the expression of the proinflammatory chemokine MCP-1 was decreased. Importantly, AngII-induced vascular remodeling was positively correlated with NADPH oxidase activity, ROS levels and MCP-1 expression levels. Notably, chronic norepinephrine infusion, which elevates blood pressure without increasing ROS production, did not induce significant vascular remodeling in WT mice. Taken together, these findings suggest that ROS elevation is required for accelerating vascular remodeling but not for hypertensive effects in this model. We demonstrated that TLR4 plays a pivotal role in regulating AngII-induced vascular ROS levels by inhibiting the expression and activity of the antioxidant enzyme ecSOD, as well as by activating NADPH oxidase, which enhances inflammation to facilitate the progression of vascular remodeling.

Aim Angiotensin II (AngII) produces reactive oxygen species (ROS), thus contributing to the development of cardiac hypertrophy and subsequent heart failure, and stimulates the expression of monocyte chemoattractant protein-1 (MCP-1). In addition, Toll-like receptor 4 (TLR4) is involved in the upregulation of MCP-1. In order to clarify whether TLR4 is involved in the onset of cardiac dysfunction caused by AngII stimulation, we investigated the effects of TLR4 on oxidative stress, the MCP-1 expression and cardiac dysfunction in mice with AngII-induced hypertension. Methods TLR4-deficient (Tlr4lPS-d) and wild-type (WT) mice were randomized into groups treated with AngII, norepinephrine (NE) or a subdepressor dose of the AngII receptor blocker irbesartan (IRB) and Angll for two weeks. Results AngII and NE similarly increased systolic blood pressure in all drug-treated groups compared to that observed in the control group among both WT and T1r4lps-d mice (p< 0.05). In the WT mice, AngII induced cardiac hypertrophy as well as vascular remodeling and perivascular fibrosis of the intramyocardial arteries and monocyte/macrophage infiltration in the heart (P<0.05). Furthermore, AngII treatment decreased the left ventricular diastolic function and resulted in a greater left ventricular end-systolic dimension (P<0.05) in addition to producing a five-fold increase in the NADPH oxidase activity, ROS content and MCP-1 expression (P<0.05). In contrast, the Tlr4lps-d mice showed little effects of AngII on these indices. In the WT mice, IRB treatment reversed these changes compared to that seen in the mice treated with AngII alone. NE produced little effect on any of the indices in either the WT or T1r4lps-d mice. Conclusions TLR4 may be involved in the processes underlying the increased oxidative stress, selectively activated MCP-1 expression and cardiac hypertrophy and dysfunction seen in cases of AngII-induced hypertension.