Transthyretin (TTR) is a binding protein involved in the tissue distribution of thyroid hormones. In preeclampsia, the elevated release of soluble endoglin (sEng) triggered by trophoblast stress plays a significant role in maternal vascular dysfunction. Previously, we demonstrated that TTR can bind to sEng and facilitate its uptake into hepatocytes [1]. Cigarette smoking during pregnancy reduces the risk of developing preeclampsia [2]. Nicotine, the main addictive component of cigarette smoke, has been shown to increase TTR expression in the brain [3], as well as alter the binding between T4 and TTR [4].
We sought to determine if nicotine affected hepatocyte expression, secretion or uptake of TTR or altered the interaction between TTR and sEng. Nicotine treatment increased TTR mRNA and protein levels in cultured HepG2 cells. Live cell uptake of fluorescently labelled TTR and sEng was measured using an Essen incucyte incubator. TTR uptake was significantly increased in the presence of nicotine. sEng uptake was significantly increased in the presence of TTR ± nicotine but not by nicotine alone. Knockdown of low-density lipoprotein receptor related protein-1 (LRP1) using esiRNA resulted in a reduced uptake of TTR-sEng. LRP1 protein levels were unaffected in nicotine treated HepG2 cells.
Nicotine may abrogate the onset of preeclampsia by increasing hepatic TTR turnover and ‘mopping up’ excess sEng in the maternal circulation thus preventing vascular dysfunction. Further research is required to better understand the role of transthyretin and nicotine in mitigating preeclampsia.