If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Adult male mice exposed to preeclampsia in utero develop elevated blood pressure (BP) and decreased endothelium dependent relaxation compared to controls, most evident at 6 months of age, while female offspring do not. We previously showed that prenatal pravastatin prevented these changes. Lectin-like oxidized low density lipoprotein receptor 1 (LOX-1) is an endothelial cell receptor that is upregulated under inflammatory and oxidative conditions, and is associated with hypertension. Our objective was to evaluate the role of LOX-1 in these gender-specific phenotypic changes, and its response to prenatal pravastatin treatment, using a well-established animal model of preeclampsia.
CD-1 mice were injected with Adv-sFlt-1 and randomly allocated to pravastatin (sFlt-prav) or water (sFlt) until weaning. A control group was injected with adenovirus carrying the murine immunoglobulin G2α Fc fragment (mFc). Offspring were sacrificed at 3 and 6 months. RNA was extracted from the aorta, and mRNA expression of LOX-1 was measured using quantitative RT-PCR. Statistical analysis was performed using ANOVA and Student t tests.
There were no differences in LOX-1 mRNA expression between groups or gender at 3 months. At 6 months, LOX-1 mRNA in sFlt offspring was upregulated by more than 2 folds compared to mFc controls (p=0.01). Prenatal pravastatin reduced the mRNA to a level not significantly different from either sFlt-1 or control (Figure). In addition, at 6 months male offspring had significantly higher LOX-1 mRNA compared with females (6.25±0.87 vs 3.19±0.36, p=0.01).
Increased expression of LOX-1 parallels the temporal and gender-specific changes in adult cardiovascular function observed in this animal model of fetal programming. These findings support a role for LOX-1 in the fetal programming of adult diseases induced by preeclampsia, and of its involvement, at least partially, in the beneficial effects of maternal treatment with pravastatin.