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Objectives Arresten is an endogenous anti-angiogenic peptide derived from the non-collagenous domain of collagen IV α -chain COL4A1. We previously identified COL4A1 as a maternal preeclampsia (PE) susceptibility gene and also shown increased mRNA expression of COL4A1 in PE decidual tissue (Johnson et al., 2007; Yong et al., 2014). This increased expression also significantly correlated with an earlier onset of PE, a marker of clinical severity. The study aims were to investigate the circulating levels of arresten in plasma from normotensive and PE women throughout pregnancy and correlate these levels with the clinical severity of PE. Methods Plasma samples were collected from n = 44 normotensive and n = 39 PE women from 16 to 40 weeks’ gestation with informed consent. Arresten levels were determined by semi-quantitative Western immunoblotting of plasma samples and expressed as densitometric units ±SEM (DU). Arresten levels were then correlated with several parameters of clinical severity in PE. Statistical tests used were Student’s t test with Welch’s correction and Pearson’s correlation. Significance was set at p Results Arresten levels were significantly increased in PE compared with normotensive plasma by 2.3-fold (PE: 1148 ± 163DU, n = 14 vs normotensive: 505 ± 46DU, n = 30) in the 2nd trimester. This increase was maintained during the 3rd trimester with an increase of 1.4-fold (PE: 776 ± 75DU, n = 25 vs normotensive: 568 ± 40DU, n = 14). Increased 3rd trimester levels were significantly associated with PE women requiring MgSO 4 treatment ( r = 0.46), with an increase of 1.7-fold observed (MgSO 4 required: 907 ± 101DU, n = 16 vs MgSO 4 Not required: 543 ± 55DU, n = 9). Conclusions Arresten levels were significantly increased in PE plasma from 16 weeks’ gestation, many weeks before the onset of clinical disease. Higher 3rd trimester levels were also associated with greater disease severity as indicated by a requirement for MgSO 4 treatment. Given its significant increase before the onset of clinical disease and its association with clinical severity, arresten may be useful in predicting PE and monitoring its severity. Disclosures H.E. Yong: None. P. Murthi: None. M.H. Wong: None. B. Kalionis: None. S.P. Brennecke: None. R.J. Keogh: None. |
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