Advanced glycation endproducts (AGE) are non-enzymatically glycated protein derivatives, which are formed acceleratedly under hyperglycemic conditions. Here we describe effects of AGE on the growth and function of endothelial cells (EC). When human umbilical vein EC are exposed to AGE, DNA synthesis as well as viable cell number is increased, while prostacyclin production is significantly inhibited. This is mainly mediated by the interaction between AGE and a cell surface receptor for AGE (RAGE). AGE also stimulate the growth and tube formation of microvascular EC, the key steps of angiogenesis, through an autocrine induction of vascular endothelial growth factor. Moreover, AGE increase plasminogen activatior inhibitor-1 production by microvascular EC, thus attenuating the fibrinolytic activity. The results indicate that AGE-RAGE interactions may predispose to angiogenesis and thrombogenesis, thereby leading to the development and progression of diabetic angiopathies.

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Normal platelet-endothelium interplay is a key mechanism for the prevention of intravascular thrombosis. Endothelial injury and a loss of normal endothelial function lead to platelet activation and cardiovascular events. We have proposed two models for altered platelet-endothelium interaction, i.e. endothelial injury by activated platelets and exercise-mediated 'desensitization' of platelets to endothelial anti-thrombotic substances. Cultured aortic endothelial cells exposed to aggregated platelets showed mitochondrial damage with ATP depletion and a reduction in nitric oxide (NO) release. Attenuated NO release was accompanied by impaired anti-thrombotic function, which was restored by L-arginine supplementation. Platelets, on the other hand, were desensitized to NO in a stressful condition like acute strenuous exercise. Although the mechanisms involved in the exercise-induced attenuation of platelet sensitivity to NO remain unclear, our in vitro study showed that both mechanical stress and epinephrine may contribute to the attenuation, at least in part. In conclusion, platelet-endothelium interaction is not simply an alliance of mutual benefits, but also a 'tense' relationship, especially in a diseased or stressful situation.

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To evaluate endothelial-leukocyte adhesion, we developed an adhesion technique using human umbilical vein endothelial cells (HUVECs) and U-937 cells. This technique clarified that ICAM-1 and VCAM-1 were primarily responsible for this adhesion. Using this technique, we found a low molecular weight compound that potently inhibits the adhesion through specifically suppressing the expression of VCAM-1 of HUVECs. When orally administered to mice, this compound also diminished the increase in paw thickness and in anti-bovine type II collagen (anti-BII) antibodies in mouse collagen-induced arthritis.

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There have been many histopathological studies of acute coronary syndromes (ACS). As for the relation between plaque morphology of culprit lesion and clinical background in ACS, few data are available. Purpose : We compared the incidence, morphological characteristics and clinical background associated with plaque rupture versus thrombosis in eroded plaques without rupture. Materials and Methods : We defined ACS as sudden coronary death, acute myocardial infarction, and unstable angina. One hundred twenty-two consecutive cases with intracoronary thrombi dying within one month after onset were histologically studied. After fixation at 100 mmHg, the major epicardial coronary arteries were cut transversely. All segments were studied by histological examination and morphological measurements. Results : Plaque rupture was identified in 70 lesions and erosion were in 54 lesions. The plaque rupture group had larger lipid core and smaller calcium deposits than the erosion group. Hypertensives had larger lipid core than normotensives. And diabetics had larger calcium deposits than non-diabetics. Also, smokers had larger lipid core and smaller calcium deposits than non-smokers. Conclusion : Coronary risk factors, i.e., hypertension, diabetes mellitus and smoking are associated with plaque morphology. Also, the area of the lipid core and calcium deposits of coronary arteries associated with pathogenesis of plaque thrombosis.

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Hyperchylomicronemia is known to lead a life-threatening acute pancreatitis. The major metabolic basis is a deficiency of lipoprotein lipase or apolipoprotein C-II, both of which play a critical role in the metabolism of triglyceride-rich lipoproteins. We presented two secondary chylomicronemic cases : One was already published elsewhere as autoimmune hyperchylomicronemia, in which several episodes of acute pancreatitis were demonstrated. The other was a case of unknown origin, in which both lipoprotein lipase and apolipoprotein C-II were preserved. The case had no history of acute pancreatitis, although it demonstrated coronary heart disease and atherosclerotic major artery disease. From these observation, we speculated cases with no abnormality of lipoprotein lipase or apolipoprotein C-II are less frequently suffered from acute pancreatitis, especially in Japan where fat consumption is less than that in western country.

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