Agonistic AT1 receptor autoantibodies and monocyte stimulation in hypertensive patients

Abstract Background Agonistic AT1 receptor autoantibodies (AT1-AA) have been described in hypertensive and preeclamptic patients. Furthermore, monocytes are activated in hypertensive patients. We investigated and compared the ability of angiotensin II (Ang II) and AT1-AA to stimulate monocytes from hypertensive and normotensive persons. The adhesiveness of the monocytes to endothelial cell layers, tissue factor expression, and chemiluminescence were determined. Methods Blood samples were obtained from 17 patients with essential hypertension and from 20 normotensive subjects. Peripheral blood monocytes were isolated by Dynabeads and used in adhesion experiments. Adherence assays, Western blotting, and reactive oxygen species release by chemiluminescence were done. Results Monocyte adhesion to human aortic or umbilical vein endothelial cell layers was significantly higher after stimulation with AT1-AA, compared to Ang II or no stimulation. The effect was blocked with tissue factor antibody or epitope peptide preincubation. Eposartan was partially effective in blocking the effects. Western blotting after AT1-AA or Ang II stimulation showed that the monocytes expressed tissue factor. The AT1-AA and Ang II induced significantly higher chemiluminescence in monocytes from hypertensive than control subjects. Endothelial cells, on the other hand, showed much less chemiluminescence. Conclusions These data show that monocytes can be stimulated by AT1-AA and Ang II to adhere, produce tissue factor, and probably reactive oxygen species. They underscore the importance of monocyte activation in hypertensive patients. The relevance of AT1-AA in hypertension will require further studies.