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

Angiotensin II Promotes SARS-CoV-2 Infection via Upregulation of ACE2 in Human Bronchial Cells

Blockers of the renin‐angiotensin system (RAS) have been reported to increase the angiotensin converting enzyme (ACE)2, the cellular receptor of SARS‐CoV‐2, and thus the risk and course of COVID‐19. Therefore, we investigated if angiotensin (Ang) II and RAS blockers affected ACE2 expression and SARS‐CoV‐2 infectivity in human epithelial bronchial Calu‐3 cells. By infectivity and spike‐mediated cell–cell fusion assays, we showed that Ang II acting on the angiotensin type 1 receptor markedly increased ACE2 at mRNA and protein levels, resulting in enhanced SARS‐CoV‐ 2 cell entry. These effects were abolished by irbesartan and not affected by the blockade of ACE‐1‐ mediated Ang II formation with ramipril, and of ACE2‐ mediated Ang II conversion into Ang 1‐7 with MLN‐4760. Thus, enhanced Ang II production in patients with an activated RAS might expose to a greater spread of COVID‐19 infection in lung cells. The protective action of Angiotensin type 1 receptor antagonists (ARBs) documented in these studies provides a mechanistic explanation for the lack of worse outcomes in high‐risk COVID‐19 patients on RAS blockers

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services