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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