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The endogenous apelin system is an emerging target for the regulation of cardiovascular homeostasis; however its role in pregnancy is not understood. We previously reported that total immunoreactive apelin was lower in the placenta of preeclamptic women (PRE) compared to normotensive women (NT). Since the processing of apelin precursor may yield a number of bioactive peptides, we established whether differences exist in the expression of the various molecular forms of apelin in the human placenta and whether the distribution pattern of apelin is altered in PRE. Placental samples were pooled from NT (n = 4) or PRE (n = 4) at 37–38 weeks of gestation and the apelin forms resolved by HPLC coupled to an apelin radioimmunoassay. Total apelin content was lower in the placenta of PRE compared to NT (4.2 vs. 6.1 pg/mg wet weight). The HPLC analysis revealed negligible levels of apelin-36 from the placentas of NT and PRE (NT: 0.09, PRE: 0.11 pg/mg weight). A peak of apelin-17 was detected in both NT and PRE samples, but the shorter forms of apelin were more abundant. Therefore, separation conditions were tailored to achieve greater resolution of the lower molecular weight forms of apelin. This analysis revealed that the predominant apelin in both PRE and NT placentas was pyroglutamylated apelin-13 (Pyr-apelin-13; NT: 7.1, PRE: 6.6 pg/mg weight); however, apelin-12 and apelin-13 were lower in PRE vs. NT placentas (1.8 and 22 fold, respectively). Moreover, we show that systemic infusion of apelin-13 (2 mg/kg/day) from day 13 to 20 of gestation reduced mean blood pressure (144 ± 1 vs. 163 ± 5 mmHg, n = 4–6, p < 0.01) in preeclamptic transgenic rats. Pyr-apelin-13 is the predominant endogenous isoform of apelin in both NT and PRE placentas, while apelin-13 and apelin-12 are downregulated in PRE placentas. As a novel therapeutic agent, apelin may prevent the development of preeclampsia. L.M. Yamaleyeva: None. M.C. Chappell: None. K. Brosnihan: None. L. Anton: None. N. Pirro: None. C. McGee: None. D.C. Merrill: None. H.L. Mertz: None.