Pravastatin alleviates lipopolysaccharide-induced placental TLR4 over-activation and promotes uterine arteriole remodeling without impairing rat fetal development

Abstract

Preeclampsia is associated with over-activation of the innate immune system in the placenta, in which toll-like receptor 4 (TLR4) plays an essential part. With their potent anti-inflammatory effects, statins have been suggested as potential prevention or treatment of preeclampsia, although evidence remains inadequate. Herewith, we investigated whether pravastatin could ameliorate preeclampsia-like phenotypes in a previously established lipopolysaccharide (LPS)-induced rat preeclampsia model, through targeting the TLR4/NF-κB pathway. The results showed that pravastatin reduced the blood pressure [maximum decline on gestational day (GD) 12, (101.33±2.49) mmHg vs. (118.3±1.37) mmHg, P<0.05] and urine protein level [maximum decline on GD9, (3,726.23±1,572.86) μg vs. (1,991.03±609.37) μg, P<0.05], which were elevated following LPS administration. Pravastatin also significantly reduced the rate of fetal growth restriction in LPS-treated rats (34.10% vs. 8.99%, P<0.05). Further pathological analyses suggested a restoration of normal spiral artery remodeling in preeclampsia rats by pravastatin treatment. These effects of pravastatin were associated with decreased TLR4/NF-κB protein levels in the placenta and IL-6/MCP-1 levels in serum. Additionally, no obvious abnormalities in fetal liver, brain, and kidney were found after administration of pravastatin. These results provide supportive evidence for use of pravastatin in preventing preeclampsia.

Thrombosis in COVID-19 infection: Role of platelet activation-mediated immunity

“…Valsartan (from the ARB family) has been demonstrated to decrease proinflammatory cytokine release and infarct size by inhibiting TLR4 signaling. Among statins family, Atorvastatin, Fluvastatin, Simvastatin has all shown an inhibitory effect on the reduction in vascular inflammation and the TLR4 signaling and pathway [ 104 – 106 ]. Eritoran (E5564) and TAK-242 are currently undergoing phase III clinical trials, especially for severe sepsis.…”