Determinant Role of Toll-like Receptor 4 (TLR4) on Angiotensin II in Isolated Umbilical Arteries from Normal and Gestational Diabetes Pregnant Women.

Abstract

Objective: Gestational diabetes mellitus (GDM) is a common condition that occurs during pregnancy and results in cesarean section, pre-eclampsia, and neonatal morbidity. Angiotensin II is a potent vasoconstrictor and an important determinant of uteroplacental perfusion. Toll-like receptor 4 (TLR4) was found to contribute to diabetes progression. This study aimed to determine how TLR4 activation affects the contraction mediated by angiotensin II type 1 receptor in the isolated umbilical arteries of normal and GDM women.

Methods: Angiotensin II was applied with either a TLR4 agonist or TLR4 antagonists to isolated arteries from normal and GDM umbilical cords. The changes in the angiotensin II response were expressed as the maximal contraction percentage and pD2 values. The mRNA expression levels of TLR4 and angiotensin II type 1 receptor gene were measured via quantitative  real-time polymerase chain reaction analysis.

Results: This study displayed an increased sensitivity to angiotensin II in the arteries of the GDM group compared with the normal group. The TLR4 agonist showed a synergistic effect with angiotensin II, while the TLR4 antagonists were not strongly determinant. In the GDM group, the TLR4 mRNA level is slightly higher than in the normal pregnancy group; however, no statistical difference was noted.

Conclusion: Toll-like receptor 4 may determine the vasoconstrictive effect of angiotensin II in normal and GDM umbilical arteries. Some studies showed a similar interaction as supportive. However, comprehensive animal and/or human studies are promising.