Amin Boroujerdi is interested in understanding the effects of drugs on the human body. In the summer of 2002, he began his intellectual exploration of the subject under the guidance of Dr. Krause and Dr. Duckles in the Pharmacology Department of UCI’s College of Medicine. Amin researched the novel and exciting topic of the nongenomic effects of estrogen on cerebral vessels. While conducting the project, he learned the importance of critical thinking and data analysis. Amin believes that this type of hands-on training will help him realize his goal of attaining a Ph.D. in pharmacology. When he is not running experiments, Amin enjoys reading, snowboarding, surfing, and visiting museums.

The hormone estrogen plays a significant role in the regulation of cardiovascular function. Acute effects of estrogen result in dilation of cerebral blood vessels by increasing levels of nitric oxide (NO). The hypothesis of this project is that estrogen acts without transcription to activate certain kinases, such as phosphatidylinositol-3 kinase (PI3K) and protein kinase B (Akt). This leads to increased activity of the enzyme that produces NO. Production of NO was measured in isolated cerebral blood vessels from ovariectomized female rats. Estrogen was found to increase cerebrovascular NO production within 5 min and to peak after 30 min. Immunoblot analysis of vessels treated with estrogen showed increased levels of the phosphorylated state of Akt (p-Akt) and endothelial nitric oxide (p-eNOS). Immuno precipitation studies showed that estrogen receptor alpha (ER a) is complexed with eNOS in the vessels. These results suggest that physiological levels of estrogen can rapidly increase NO levels in cerebral vesse ls through activation of the PI3K/Akt/eNOS pathway. These findings provide a better understanding of the effects of this hormone, which is important for the potential treatment for cardiovascular diseases.

Diana Krause College of Medicine

The effects of estrogen on brain blood vessels and stroke is a timely women’s health issue. Although protective actions of estrogen have been demonstrated, recent clinical trials with combination hormone replacement therapy did not show a benefit. Amin’s study identifies a new mechanism by which the major estrogen, 17ß-estradiol, affects the endothelial layer lining cerebral blood vessels. Whereas estrogen has been considered a nuclear regulator of gene expression, recent data suggest the hormone also may act rapidly to alter intracellular signaling. He tested this theory in rat cerebral blood vessels and found estrogen rapidly increased production of the vasodilator nitric oxide. While conducting research, Amin developed one-on-one relationships with graduate and postdoctoral students and faculty. He sharpened his analytical thinking skills, was awarded fellowships, and presented his work at campus symposia and a national professional meetings. Amin’s exposure to biomedical research resulted in his pursuit of a Ph.D. in pharmacology.