Alterations in vascular function by syncytiotrophoblast extracellular vesicles via LOX-1 in mouse uterine arteries

Syncytiotrophoblast extracellular vesicles (STBEVs), released into the maternal circulation during pregnancy, have been shown to affect vascular function, however, the mechanism remains unknown. In rats, STBEVs were shown to reduce endothelium-mediated vasodilation via LOX-1, a multi-ligand scavenger receptor that has been associated with vascular dysfunction. Recently, LOX-1 was shown to interact with the AT-1 receptor for angiotensin II. We hypothesized that, in pregnant mice, STBEVs would impair vascular function via LOX-1 and would specifically affect angiotensin II responses. Uterine arteries from pregnant control (C57BL/6) and LOX-1KO mice were isolated on GD18.5. Endothelium-dependent (methylcholine; ± L-NAME to assess nitric oxide contribution), and -independent (sodium nitroprusside) vasodilation, and vasoconstriction (angiotensin II; ± AT-1 [candesartan] or AT-2 [PD123.319] receptor antagonists; high potassium salt solution) responses were assessed using wire myography. AT-1 and AT-2 expression was analyzed using fluorescence microscopy. Human umbilical vein endothelial cells (HUVECs) were stimulated with STBEVs ± LOX-1 blocking antibody, and superoxide and peroxynitrite production were analyzed. Although methylcholine-induced vasodilation was decreased (p=0.0012), nitric oxide contribution to vasodilation was greater in LOX-1KO mice (p=0.0055). STBEVs delayed angiotensin II tachyphylaxis in arteries from control but not LOX-1KO mice (p<0.000...

Source: Clinical Science - October 23, 2018 Category: Biomedical Science Authors: Spaans, F., Quon, A., Rowe, S. R., Morton, J. S., Kirschenman, R., Sawamura, T., Tannetta, D. S., Sargent, I. L., Davidge, S. T. Tags: PublishAheadOfPrint Source Type: research