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Research interests:
Altered vascular cells are eminent signs of diseases including atherosclerosis (動脈硬化), hypertension (高血壓) and sepsis (敗血症) where unregulated cell death, movement and proliferaton occur. Dysregulation of the normal balance of various growth factors/cytokines, vasoactive factors, and oxidative status in vascular endothelial cells (EC) or smooth muscle cells (SMC) are central issues. Oxidized low-density-lipoprotein (oxLDL) or endotoxin (lipopolysaccharide, LPS) causes damage which estrogen and antioxidants protect EC or SMC via several different but sometimes connected mechanisms involving alterations in reactive oxygen species (ROS), nitric oxide (NO), mitogen-activated signaling (MAPK), among others. We aim to examine the interactions between such pathways, e.g., ROS and NO employing cyclic GMP (important mediator of NO’s effect) as a summation product, in cellular processes such as migration or apoptosis. The protective actions of estrogen and antioxidants are further explored by investigating the change of these pathways and the relevance of the change with the improvement of endothelial function in blood vessels.
Our approach emphasizes the integration at different levels of research. For example, to study the protective role of estrogen in cardiovascular functions we determined blood pressure/heart rate of unanesthetized rats, contraction and relaxation responses of isolated aortic segments from estrogen-treated rats with or without EC, effects of estrogen on ECs or SMCs pretreated with oxLDL (ROS response, NO production, etc.), and biochemical changes such as cyclic GMP level, mitochondrial membrane potential, apoptotic proteins, etc. It is believed that physiological significance will be illustrated in such an integrated approach.
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Publications:
1. Hsieh, C.C. and Lau, Y.T. (1998) Migration of vascular smooth muscle cells is enhanced in cultures derived from spontaneously hypertensive rat. Eur. J. Physiol. 435:286-292.
2. Chen, H.M., Shyr, M.H., Lau, Y.T. Hwang, T.L. and Chen, M.F. (1998) Leukocyte-endothelial adherence correlates with pancreatic nitric oxide production in early caerulein-induced pancreatitis in rats. Shock 10:218-222.
3. Hwang, T.L., Yang, J.T. and Lau, Y.T. (1999) Arginine-nitric oxide pathway in plasma membrane of rat hepatocytes during early and late sepsis. Crit. Care Med. 27:137-141.
4. Lo, C.C., Chen, J.C., Chen, H.M., Shyr, M.H., Lau, Y.T., Lin, J.N., Chen, M.F. (1999) Aminoguanidine attenuates hemodynamic and microcirculatory derangement in rat intestinal ischemia and reperfusion. J Trauma: Injury, Infection, and Critical Care 47:1108-1113.
5. Hsieh, C.C., Yen, M.H., Liu, H.W. and Lau, Y.T. (2000) Lysophosphatidylcholine induces apoptotic and non-apoptotic death in vascular smooth muscle cells: in comparison with oxidized LDL. Atherosclerosis 151:481-491.
6. Hsieh, C.C., Yen, M.H., Yen, C.H. and Lau, Y.T. (2001) Oxidized low density lipoprotein induces apoptosis via generation of reactive oxygen species in vascular smoth muscle cells. Cardiovasc Res 49(1):135-145.
7. Yen, C.H., Hsieh, C.C., Chou, S.Y. and Lau, Y.T. (2001) 17β-Estradiol inhibits oxidized low density lipoprotein-induced generation of reactive oxygen species in endothelial cells. Life Sci 70(4):403-413.
8. Yen, C.H., Lau, Y.T. (2002) Vascular responses in male and female hypertensive rats with hyperhomocysteinemia. Hypertension 40:322-328.
9. Lau, Y.T. (2002) Receptor-dependent and genomic-independent actions of estrogen in vascular protection. Chang Gung Med J 25:636-644.
10. Hsieh CC, Hwang TL, Chen HM, Chen MF, Sun YF, Lau YT. (2003) Sepsis Correlated With Increased Erythrocyte Na+ Content and Na+-K+ Pump Activity. J Biomed Sci 10(4):389-395.
11. Wang YR, Yen CH, Sun YF, Lau YT. (2003) Gender-dependent Response in Blood Pressure Changes Following the Inhibition of Nitric Oxide Synthase. Chinese J Physiol 46(2):91-94.
12. Tsen CM, Hsieh CC, Yen CH, Lau YT. (2003) Homocysteine Altered ROS Generation and NO Accumulation in Endothelial Cells. Chinese J Physiol 46(3):129-136.
13. Yen CH, Lau YT. (2004) 17β-oestradiol enhances aortic endothelium function and smooth muscle contraction in male spontaneously hypertensive rats. Clin Sci 106(5):541-546.
14. Lau YT. Problem-based learning in pharmacology: a survey of department heads in Taiwan. Acta Pharmacol Sin. 2004;25(9):1239-1241.
15. Yen CH, Wang YR, Huang CF and Lau YT. Estrogen ameliorates Nω-nitro-L-arginine methyl ester-induced blood pressure increment in male spontaneously hypertensive rats: the role of cGMP. Chinese J Physiol. 2004;47(4):183-187.
16. Yu HP, Lui PW, Hwang TL, Yen CH and Lau YT. Propofol improves endothelial dysfunction and attenuates vascular superoxide production in septic rats. Critical Care Medicine. 2006;34:453-460.
17. Hsieh HL, Wu CB, Sun CC, Liao CH Lau YT and Yang CM. Sphingosine-1-phosphate induced COX-2 expression via PI3K/Akt and p42/p44 MAPK pathways in rat vascular smooth muscle cells. J Cell Physiol. 2006;207:757-766.
18. Huang CF, Wang YR, Yen CH, Chou SH and Lau YT. Paraquat-Induced Lipid Peroxidation:Effects of Ovariectomy and Estrogen Receptor Antagonis. Chinese J Physiol. 2006;49(3):141-146.
19. Tsai CC and Lau YT. Diversified teaching methods of medical physiology: effects on examination-forced study. 2006;6(9):659-661.
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