Aldosterone Biosynthesis Is Potently Stimulated by Perfluoroalkyl Acids: A Link between Common Environmental Pollutants and Arterial Hypertension

The large environmental contamination of drinking water by perfluoroalkyl substances (PFAS) markedly increased the plasma levels of pentadecafluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in a Northern Italy population with a high prevalence of arterial hypertension and cardiovascular disease. As the link between PFAS and arterial hypertension is unknown, we investigated if they enhance the biosynthesis of the well-known pressor hormone aldosterone. We found that PFAS increased aldosterone synthase (CYP11B2) gene expression by three-fold and doubled aldosterone secretion and cell and mitochondria reactive oxygen species (ROS) production over controls (p < 0.01 for all) in human adrenocortical carcinoma cells HAC15. They also enhanced the effects of Ang II on CYP11B2 mRNA and aldosterone secretion (p < 0.01 for all). Moreover, when added 1 h before, the ROS scavenger tempol abolished the effect of PFAS on CYP11B2 gene expression. These results indicate that at concentrations mimicking those found in human plasma of exposed individuals, PFAS are potent disruptors of human adrenocortical cell function, and might act as causative factors of human arterial hypertension via increased aldosterone production.

Automated summary

In a Northern Italy population with a high prevalence of arterial hypertension and cardiovascular disease, the contamination of drinking water with perfluoroalkyl substances (PFAS) significantly increased the levels of pentadecafluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) in the plasma. It was investigated whether PFAS enhance the biosynthesis of aldosterone, a known pressor hormone. The study found that PFAS significantly increased the expression of the aldosterone synthase gene, doubled aldosterone secretion, and caused an increase in cellular and mitochondrial production of reactive oxygen species (ROS) in human adrenocortical carcinoma cells. These findings suggest that PFAS may contribute to the development of arterial hypertension through increased aldosterone production.