Endothelial Dysfunction and Insulin Resistance as Pathophysiologic Mechanisms in a Rat Model of Preeclampsia

2010 American Journal of Biochemistry and Biotechnology  
Problem statement: To assess the plasma concentrations and placental gene expression of soluble fms like tyrosine kinase (sFlt-1), Vascular Endothelial Growth Factor (VEGF), visfatin and Tumour Necrosis Factor α (TNFα) in a rat model of preeclampsia, induced by chronic Reduction of Uterine Perfusion Pressure (RUPP) and to investigate the involvement of Insulin Resistance (IR) in the pathophysiology of preeclampsia and the possible relation of visfatin and TNFα to IR in preclampsia. Approach:
more » ... nty female Sprague-Dawley rats weighing 220-250 g were divided into either RUPP (n = 10) or Normal Pregnant (NP; n = 10) (control) groups. Plasma levels and placental gene expression of sFlt-1, VEGF, visfatin, TNFα, plasma endothelin (ET-1), glucose, serum insulin, creatinine, HOMA-IR and placental Malondialdehyde (MDA) and total antioxidants were measured. Also, Mean Arterial Pressure (MAP), fetal number and weight were determined. Results: In RUPP rats, MAP increased, plasma level and placental gene expression of sFlt-1, visfatin and TNFα increased while those of VEGF decreased. Moreover, plasma ET-1, glucose, insulin, HOMA-IR increased while GFR, fetal weight and number decreased. There is a significant positive correlation between TNFα, ET-1, sFlt-1 and MAP, between plasma visfatin or TNFα levels and both serum insulin and HOMA-IR, between visfatin and TNFα, between TNFα and ET-1 and between placental MDA and either sFlt-1 or ET-1. Furthermore, a negative correlation was reported between VEGF and MAP. Conclusion: RUPP increased sFlt-1, TNFα and decreased VEGF resulting in endothelial dysfunction which is manifested by increased MDA and ET-1. This results in altered renal function and hypertension. Moreover, IR may be involved in the pathophysiology of preeclampsia. Visfatin and TNFα, may have a role in IR during preclampsia.
doi:10.3844/ajbbsp.2010.172.180 fatcat:tuv6fn7kmjfr3dbvv3g5nmo5b4