BackgroundPregnancy is associated with higher maternal serum concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in spite of hyperestrogenemia, which in the non-pregnant state is associated with lower TC and LDL-C levels. It is unknown whether proprotein convertase subtilisin kexin 9 (PCSK9) plays a role in the elevation of LDL-C during pregnancy. PCSK9 promotes the post-translational degradation of the LDL receptor on the cell surface, thereby inhibiting clearance of LDL-C in circulation. Our study assessed whether serum PCSK9 concentrations change in third trimester pregnancy when compared to non-pregnant healthy women.MethodsMaternal serum was collected at the time of delivery from women with normal pregnancy, pre-eclampsia (PET) and intrauterine growth restriction (IUGR). Paired umbilical cord blood was also collected for analysis. Serum lipids and PCSK9 were measured in the collected samples.ResultsCompared to the non-pregnant state, serum PCSK9 was significantly higher in third trimester pregnancy (554±223 versus 342±177 ng/ml for normal pregnancy; 513±189 versus 342±177 ng/ml for PET; and 525±157 versus 342±177 ng/ml for IUGR) (p<0.0001). Umbilical cord blood levels of PCSK9 were much lower than maternal blood levels (538±184 versus 306±135 ng/ml; p<0.0001).ConclusionOur study provides the first observation of a significant increase in circulating PCSK9 in pregnancy compared to the non-pregnant state. The same degree of PCSK9 elevation was seen in pregnancies complicated by PET and IUGR as in normal pregnancy. Our findings raise the possibility that PCSK9 may mediate the LDL-C elevation associated with pregnancy.HSFC BackgroundPregnancy is associated with higher maternal serum concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in spite of hyperestrogenemia, which in the non-pregnant state is associated with lower TC and LDL-C levels. It is unknown whether proprotein convertase subtilisin kexin 9 (PCSK9) plays a role in the elevation of LDL-C during pregnancy. PCSK9 promotes the post-translational degradation of the LDL receptor on the cell surface, thereby inhibiting clearance of LDL-C in circulation. Our study assessed whether serum PCSK9 concentrations change in third trimester pregnancy when compared to non-pregnant healthy women. Pregnancy is associated with higher maternal serum concentrations of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) in spite of hyperestrogenemia, which in the non-pregnant state is associated with lower TC and LDL-C levels. It is unknown whether proprotein convertase subtilisin kexin 9 (PCSK9) plays a role in the elevation of LDL-C during pregnancy. PCSK9 promotes the post-translational degradation of the LDL receptor on the cell surface, thereby inhibiting clearance of LDL-C in circulation. Our study assessed whether serum PCSK9 concentrations change in third trimester pregnancy when compared to non-pregnant healthy women. MethodsMaternal serum was collected at the time of delivery from women with normal pregnancy, pre-eclampsia (PET) and intrauterine growth restriction (IUGR). Paired umbilical cord blood was also collected for analysis. Serum lipids and PCSK9 were measured in the collected samples. Maternal serum was collected at the time of delivery from women with normal pregnancy, pre-eclampsia (PET) and intrauterine growth restriction (IUGR). Paired umbilical cord blood was also collected for analysis. Serum lipids and PCSK9 were measured in the collected samples. ResultsCompared to the non-pregnant state, serum PCSK9 was significantly higher in third trimester pregnancy (554±223 versus 342±177 ng/ml for normal pregnancy; 513±189 versus 342±177 ng/ml for PET; and 525±157 versus 342±177 ng/ml for IUGR) (p<0.0001). Umbilical cord blood levels of PCSK9 were much lower than maternal blood levels (538±184 versus 306±135 ng/ml; p<0.0001). Compared to the non-pregnant state, serum PCSK9 was significantly higher in third trimester pregnancy (554±223 versus 342±177 ng/ml for normal pregnancy; 513±189 versus 342±177 ng/ml for PET; and 525±157 versus 342±177 ng/ml for IUGR) (p<0.0001). Umbilical cord blood levels of PCSK9 were much lower than maternal blood levels (538±184 versus 306±135 ng/ml; p<0.0001). ConclusionOur study provides the first observation of a significant increase in circulating PCSK9 in pregnancy compared to the non-pregnant state. The same degree of PCSK9 elevation was seen in pregnancies complicated by PET and IUGR as in normal pregnancy. Our findings raise the possibility that PCSK9 may mediate the LDL-C elevation associated with pregnancy.HSFC Our study provides the first observation of a significant increase in circulating PCSK9 in pregnancy compared to the non-pregnant state. The same degree of PCSK9 elevation was seen in pregnancies complicated by PET and IUGR as in normal pregnancy. Our findings raise the possibility that PCSK9 may mediate the LDL-C elevation associated with pregnancy.