Molecular Pathophysiology

Staff List

Summary of Activity

Our goal is to elucidate the physiological, and pathophysiological mechanisms of vascular function and its disruption through investigating the biology of endothelial cells. In the process, we have found a key molecule, LOX-1, which might illustrate the pathophysiology of atherothrombotic disease. Since the vascular function is closely related to ageing-related malfunctioning of organs, the finding opened a new avenue for understanding ageing-related diseases. Based on the clues, we are developing novel diagnostic, preventive and therapeutic methods.

Research Subject

• ?Biological significance of LOX-1 gene family
• ?Screening of LOX-1 blocker to realize a novel therapeutics
• ?Development of novel diagnostic technologies for clinical application of our research
• ?Mechanism of ageing and ageing-related diseases

Outlook for Research

The basic research has significance in itself, clarifying the mechanism of nature. Besides, important as well is the application of the novel knowledge and technologies to the future of medicine and people’s happiness.
Our study is to contribute to medical diagnosis and therapeutics of lifestyle-related diseases, preventing ageing of vasculature and realizing healthy longevity.

Major Publications

1. Chan, H.C., Ke, L.Y., Chu, C.S., Lee, A.S., Shen, M.Y., Cruz, M.A., Hsu, J.F., Cheng, K.H., Chan, H.C., Lu, J., Lai, W.T., Sawamura, T., Sheu, S.H., Yen, J.H. and Chen, C.H.: Highly electronegative LDL from patients with ST-elevation myocardial infarction triggers platelet activation and aggregation. Blood, 2013, 122:3632-3641.

2. Fujita, Y., Yamaguchi, S., Kakino, A., Iwamoto, S., Yoshimoto, R. and Sawamura, T.: Lectin-like oxidized LDL receptor 1 is involved in CRP-mediated complement activation. Clin Chem, 2011, 57:1398-1405.

3. Inoue, N., Okamura, T., Kokubo, Y., Fujita, Y., Sato, Y., Nakanishi, M., Yanagida, K., Kakino, A., Iwamoto, S., Watanabe, M., Ogura, S., Otsui, K., Matsuda, H., Uchida, K., Yoshimoto, R. and Sawamura, T.: LOX index, a novel predictive biochemical marker for coronary heart disease and stroke. Clin Chem, 2010, 56:550-558.

4. Fujita, Y., Kakino, A., Nishimichi, N., Yamaguchi, S., Sato, Y., Machida, S., Cominacini, L., Delneste, Y., Matsuda, H. and Sawamura, T.: Oxidized LDL receptor LOX-1 binds to C-reactive protein and mediates its vascular effects. Clin Chem, 2009, 55:285-294.

5. Mehta, J.L., Sanada, N., Hu, C.P., Chen, J., Dandapat, A., Sugawara, F., Satoh, H., Inoue, K., Kawase, Y., Jishage, K., Suzuki, H., Takeya, M., Schnackenberg, L., Beger, R., Hermonat, P.L., Thomas, M. and Sawamura, T.: Deletion of LOX-1 reduces atherogenesis in LDLR knockout mice fed high cholesterol diet. Circ Res, 2007, 100:1634-1642.

6. Inoue, K., Arai, Y., Kurihara, H., Kita, T. and Sawamura, T.: Overexpression of lectin-like oxidized low-density lipoprotein receptor-1 induces intramyocardial vasculopathy in apolipoprotein E-null mice. Circ Res, 2005, 97:176-184.

7. Honjo, M., Nakamura, K., Yamashiro, K., Kiryu, J., Tanihara, H., McEvoy, L.M., Honda, Y., Butcher, E.C., Masaki, T. and Sawamura, T.: Lectin-like oxidized LDL receptor-1 is a cell-adhesion molecule involved in endotoxin-induced inflammation. Proc Natl Acad Sci U S A, 2003, 100:1274-1279.

8. Kakutani, M., Masaki, T. and Sawamura, T.*: A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1. Proc Natl Acad Sci U S A, 2000, 97:360-364.

9. Oka, K., Sawamura, T., Kikuta, K., Itokawa, S., Kume, N., Kita, T. and Masaki, T.: Lectin-like oxidized low-density lipoprotein receptor 1 mediates phagocytosis of aged/apoptotic cells in endothelial cells. Proc Natl Acad Sci U S A, 1998, 95:9535-9540.

10. Sawamura, T., Kume, N., Aoyama, T., Moriwaki, H., Hoshikawa, H., Aiba, Y., Tanaka, T., Miwa, S., Katsura, Y., Kita, T. and Masaki, T.: An endothelial receptor for oxidized low-density lipoprotein. Nature, 1997, 386:73-77.