We are conducting research in the field of thrombosis and hematostasis for the prevention of vascular disorders, such as cerebral vascular and coronary heart diseases, from the viewpoint of dietary control. To apply food science research to vascular thrombosis, we have focused on changes in the function of endothelial cells under various physiological conditions with fluctuations in the secretion of adipocytokines (adiponectin and PAI-1) from adipose tissues. Our studies address the control of the following through diet: 1) imbalances between pro- and anti-coagulant activities of endothelium under the pathological conditions such as inflammation, sepsis, atherogenesis, and neoplasm; 2) anomalous secretions of adipocytokines under pro-thrombotic conditions; 3) irregular circadian rhythms of thrombomodulin in the metabolic syndrome. We believe that “eating regularly every morning” is the key to reducing thrombosis and relative vascular disorders. Further, our new project demonstrates the defensive function of the endothelial surface against tumor metastasis. 
Original paper Ketogenic diet disrupts the circadian clock and increases hypofibrinolytic risk by inducing expression of plasminogen activator inhibitor-1: Oishi, K., Uchida, D., Ohkura, N., Doi, R., Ishida, N., Kadota, K., Horie, S.: Arterioscler. Thromb.Vasc.Biol. 29, 1571-1577 (2009). CLOCK regulates circadian platelet activity: Ohkura, N., Oishi, K., Sudo, T., Hayashi, H., Shikata, K., Ishida, N., Matsuda, J., Horie, S.: Thromb Res. (2008). Thrombomodulin is a clock-controlled gene in vascular endothelial cells: Takeda, N., Maemura, K., Horie, S., Oishi, K., Imai, Y., Harada, T., Saito, T., Shiga, T., Amiya, E., Manabe, I., Ishida, N., Nagai, R.: J.Biol.Chem., 282, 32561-7 (2007). Circadian variations in coagulation and fibrinolytic factors among four different strains of mice: Ohkura, N., Oishi, K., Sakata, T., Kadota, K., Kasamatsu, M., Fukushima, N., Kurata, A., Tamai, Y., Shirai, H., Atsumi, G., Ishida, N., Matsuda, J., Horie, S.: Chronobiol Int., 24, 651-69 (2007). Comparative study of circadian variation in numbers of peripheral blood cells among mouse strains: Unique feature of C3H/HeN mice: Ohkura, N., Oishi, K., Sekine, Y., Atsumi, G., Ishida, N., Matsuda, J., Horie, S.: Biol.Pharm.Bull. 30, 1177-80 (2007). Clock mutation affects circadian regulation of circulating blood cells: Oishi, K., Ohkura, N., Kadota, K., Kasamatsu, M., Shibusawa, K., Matsuda, J., Machida, K., Horie, S., Ishida, N.: J.Circadian Rhythms 4, 13-19 (2006). Circadian clock molecules CLOCK and CRYs modulate fibrinolytic activity by regulating the PAI-1 gene expression: Ohkura, N., Oishi, K., Fukushima, N., Kasamatsu, M., Atsumi, G., Ishida, N., Horie, S., Matsuda, J.: J.Thromb.Haemost. 4, 2478-2485 (2006). Verotoxin-1 stimulation of macrophage-like THP-1 cells up-regulates tissue factor expression through activation of c-Yes tyrosine kinase: Possible signal transduction in tissue factor up-regulation: Murata, K., Higuchi, T., Takada, K., Oida, K., Horie, S., Ishii, H.: Biochim.Biophys.Acta 1762, 835-843 (2006). Tissue-specific augmentation of circadian PAI-1 expression in mice with streptozotocin-induced diabetes: Oishi, K., Ohkura, N., Kasamatsu, M., Fukushima, N., Shirai, H., Matsuda, J., Horie, S., Ishida, N.: Thromb.Res. 114, 129-135 (2004). Oxidized phospholipids in oxidized low-density lipoprotein reduce the activity of tissue factor pathway inhibitor through association with its carboxy-terminal region: Ohkura, N., Hiraishi, S., Itabe, H., Hamuro, T., Kamikubo, Y., Takana, T., Matsuda, J.,Horie, S.: Antioxid. Red. Signal. 6, 705-712 (2004). |
