RESUMO
BACKGROUND: Preeclampsia is characterized by a new onset of hypertension during pregnancy and is associated with autoantibodies against the angiotensin II type 1 receptor and oxidative stress. There is growing evidence for mitochondrial dysfunction in preeclampsia, however, the culprits for mitochondrial dysfunction are still being defined. We previously demonstrated that angiotensin II type 1 autoantibodies cause renal, placental, and endothelial mitochondrial dysfunction in pregnant rats. However, the role of the angiotensin II type 1 autoantibodies in endothelial mitochondrial function in response to sera from preeclamptics is unknown. Thus, we hypothesized that circulating factors, such as the angiotensin II type 1 autoantibodies, during preeclampsia would negatively impact the vascular endothelial mitochondrial function in human umbilical vein endothelial cells. OBJECTIVE: The objective of the study was to determine a role for circulating angiotensin II type 1 autoantibodies to cause endothelial mitochondrial reactive oxygen species and dysfunction in preeclampsia compared to normal pregnant controls. STUDY DESIGN: Immediately after delivery, sera was collected from preeclamptic patients and normal pregnant controls. The mitochondrial reactive oxygen species were determined from the cells treated overnight with 10% sera from either the control or preeclamptic patients with and without the antiotension II type 1 autoantibodies inhibitor peptide ('n7AAc'). RESULTS: Preeclampsia patients at <34 weeks' gestation exhibited an elevated mean arterial blood pressure. Cells treated with serum from the preeclampsia patients at <34 weeks gestational age showed significantly (P<0.05) greater mitochondrial oxidative stress and reduced respiration than cells treated with the control sera, and these abnormalities were restored with 'n7AAc'. CONCLUSION: This study demonstrates that endothelial mitochondrial dysfunction occurs in response to circulating factors, especially in response to serum from preterm preeclampsia patients, and can be restored by blocking circulating angiotensin II type 1 autoantibodies, thereby indicating a potential new therapeutic target for preeclampsia.
