Impact of obesity on angiogenic and inflammatory markers in the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) cohort

Abstract

BACKGROUND: While several studies have demonstrated that obesity increases the risk of preeclampsia (PE), the mechanisms have yet to be elucidated. We assessed the association between maternal/paternal obesity and PE and hypothesised that maternal body mass index (BMI) would be associated with an adverse inflammatory and angiogenic profile. High-sensitivity C-reactive protein (hs-CRP) and following serum angiogenic markers were determined: soluble endoglin (sEng), soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF). METHODS: Data on BMI were available from 1450 pregnant women with PE and 1065 without PE. Serum concentrations of hs-CRP and angiogenic markers were available from a subset at first and third trimesters. RESULTS: Prepregnancy BMI was higher in the PE group than in controls (mean±SD) 25.3±5.2 vs. 24.1±4,4, p<0.001, adjusted for parity, mother's age and smoking status before pregnancy. Increased hs-CRP concentrations were observed in both PE and non-PE women similarly according to BMI category. In women with PE, a higher BMI was associated with lower sFlt-1 and sEng concentrations throughout the pregnancy (p=0.004, p=0.008, respectively). There were no differences in PlGF in PE women according to BMI. CONCLUSIONS: We confirmed increased pre-pregnancy BMI in women with PE. Enhanced inflammatory state was confirmed in all women with overweight/obesity. Partly paradoxically we observed that PE women with obesity had less disturbed levels of angiogenic markers than normal weight women with PE. This should be taken account when angiogenic markers are used in PE prediction.

The Immunogenetic Conundrum of Preeclampsia

“…Herse and coworkers have also shown that TNFα decreased sFLT1 expression in mature adipocytes ( 81 ). We and others have found lower concentration of sFLT1 in obese compared to normal-weight preeclamptic women, but not in respective normotensive pregnant women ( 82 , 83 ). Associations between maternal body mass index and proinflammatory cytokines TNFα and MCP-1 in maternal plasma have been demonstrated ( 84 ).…”

Obesity and Preeclampsia: Common Pathophysiological Mechanisms

“…Moreover, as discussed above, proinflammatory adipokines induces endothelial dysfunction. Recently, the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC) cohort have confirmed the women that developed preeclampsia have increased pre-pregnancy BMI and altered inflammatory markers (Jääskeläinen et al, 2018). Leptin, another adipokine that is increased in obesity, induces activation of the NADPH oxidase, which impairs endothelium-dependent vasodilatation by increasing NO degradation (Fortuño et al, 2010).…”

High-fat diet from parental generation exaggerates body and adipose tissue weights in pregnant offspring

“…Recall that the P-HFD/F1-HFD group also had some of the highest body fat weights detected in this study. Human studies have shown a negative association of body weight and circulating levels of the anti-hypertensive factor, PlGF [15,16]. As PlGF is critically important for proper blood pressure regulation in pregnancy, correlative statistics were performed to assess whether PlGF concentrations were associated with blood pressure levels.…”

“…PlGF is important for proper endothelial and vascular function and blood pressure regulation during pregnancy [ 12 – 14 ]. Because PlGF is negatively associated with body weight in pregnant women [ 15 , 16 ], it was assessed whether PlGF levels were altered in response to HFD in the pregnant offspring groups in this study.…”