3 research outputs found
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 reninâangiotensin system (RAS) have been reported to increase the angiotensin
converting enzyme (ACE)2, the cellular receptor of SARSâCoVâ2, and thus the risk and course
of COVIDâ19. Therefore, we investigated if angiotensin (Ang) II and RAS blockers affected ACE2
expression and SARSâCoVâ2 infectivity in human epithelial bronchial Caluâ3 cells. By infectivity
and spikeâmediated cellâcell 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 SARSâCoVâ
2 cell entry. These effects were abolished by irbesartan and not affected by the blockade of ACEâ1â
mediated Ang II formation with ramipril, and of ACE2â mediated Ang II conversion into Ang 1â7
with MLNâ4760. Thus, enhanced Ang II production in patients with an activated RAS might expose
to a greater spread of COVIDâ19 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 highârisk COVIDâ19 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