The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Biochemistry and Molecular Biology
ANGIOTENSIN RECEPTORS, AUTOANTIBODIES, & DISEASE
Angiotensin receptor activating autoantibodies and preeclampsia.
Preeclampsia is the leading cause of death due to pregnancy with clinical consequences involving severe life-threatening vascular abnormalities. The molecular mechanisms responsible for the pathogenesis of preeclampsia remain poorly understood. We found that women with preeclampsia harbor autoantibodies capable of activating the angiotensin receptor, AT1R. We showed that these autoantibodies bind to a specific seven amino acid sequence on the second extracellular loop of the angiotensin receptor. Overall, our results provide strong evidence that these autoantibodies activate AT1 receptors on a variety of cells and thereby contribute to many features of the disease. Research is underway to determine the immunological origin of these autoantibodies and the mechanism by which they activate the AT1 receptor. This project is being carried out in collaboration with Dr. Yang Xia.
Angiotensin receptor activating autoantibodies (AT1-AAs) may underlie many features of preeclampsia. AT1-AAs from preeclamptic patients activate angiotensin receptors (AT1R) on the surface of many cell types and may be responsible for many features of this serious pregnancy disorder. We have shown that antibody-induced receptor activation results in the mobilization of intracellular calcium and the activation of many genes. We propose that AT1-AAs activate AT1 receptors by promoting receptor homodimerization. ROS, reactive oxygen species. SMC, smooth muscle cells; EC, endothelial cells.
Education & Training
Ph.D. - Princeton University - 1974
Autoimmune hypertension: Angiotensin receptor activating autoantibodies