RhACE2 – playing an important role in inhibiting apoptosis induced by Ang II in HUVECs

Abstract

Background: Henoch-Schonlein purpura (HSP) is a common hemorrhagic disease, which manifests the inflammation in the body's most microvasculars. Angiotensin II (Ang II) can induce the damage and apoptosis of vascular endothelial cells while angiotensin converting enzyme 2 (ACE2) can antagonist the action of Ang II. However, the effect of ACE2 on Ang II-induced endothelial damage remains unknown. Objective: To evaluate the effect of recombinant human angiotensin converting enzyme 2 (rhACE2) on the Ang II-induced damage of human umbilical vein endothelial cells (HUVECs) and the release of inflammatory mediator in vitro. Methods: Cultured HUVECs were randomly divided into 6 groups: the control group, rhACE2 group, Ang II group, and Ang II+ rhACE2 groups (3 subgroups). The cell vitality, cell cycle, apoptosis rate of the HUVECs and the levels of reactive oxygen species (ROS), interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) and lactate dehydrogenase (LDH) were measured, respectively. Results: Compared with the control group, the cell viability and the rate of S phase cells in Ang II group significantly decreased ( P < .05) while the apoptosis percentage and the levels of ROS, IL-8, TNF-α, TGF-β1, and LDH in Ang II group significantly increased ( P < .05). There were no significant differences between the control group and rhACE2 group. Compared with the Ang II group, the cell viability and the rate of S phase cells in Ang II+rhACE2 groups were higher ( P < .05) and the apoptosis percentage, the level of ROS, IL-8, TNF-α, TGF-β1, LDH in Ang II+rhACE2 groups were lower ( P < .05). Conclusions: Ang II can induce the apoptosis of HUVECs and the release of inflammatory mediator, while rhACE2 can inhibit the detrimental effects of Ang II. The results of this study suggest that rhACE2 has a protective effect on HSP, which is probably a new way for the prevention and treatment of HSP.

Game of “crowning” season 8: RAS and reproductive hormones in COVID-19 – can we end this viral series?

“…Disruption of the depressor arm, the ACE2/Ang-(1-7)/MasR, and AT 2 R will lead to exacerbation of the effects of the pressor arm, the ACE/AngII/AT 1 R pathway, which seems to be responsible for the decompensation of pre-existent comorbidities in coronavirus disease 2019 (COVID-19) patients where the highest fatality is reported [ 13 ]. The resulting Ang-II increased levels lead to cell apoptosis with the release of proinflammatory cytokines [ 14 ]. This stimulates adaptive immune responses with the possibility of triggering a cytokine storm from its excessive activation [ 15 ].…”

Vasculopathy and Coagulopathy Associated with SARS-CoV-2 Infection

“…Consistent with these results, recombinant human ACE2 protected primary human endothelial cells from death induced by angiotensin II [51], and stimulation of endogenous ACE2 in human coronary arterial endothelial cells inhibited NF-kB signaling and reduced TNFα activity [52]. Similarly, adenoviral transduction of ACE2 or administration of angiotensin 1-7 reduced reactive oxygen species (ROS) production in endothelial cells and rescued endothelial cell function in diabetic mice [53].…”

Multiple potential targets of opioids in the treatment of acute respiratory distress syndrome from COVID‐19

“…Most of the pathology is induced by the immune response against the invading pathogen rather than the infection itself as the virus uses the replicative machinery of the cell followed by budding for its egress rather than cell lysis 45 . The host cell death can occur if excess Ang II is produced leading to direct apoptosis 46 and when excess protein is produced with endoplasmic reticulum (ER) stress, unfolded protein response (UPR) and subsequent apoptosis 47 . Whether a link exists between the antifibrotic and antiinflamatory effects of the depressor arm of RAS with the ACE2 receptors and the antiinflamatory and antifibrotic effects from stimulating opioid receptors in the immune system remains elusive but could represent a future research direction as both receptors are abundant in the brain and peripheral organs and exert seemingly inter‐related effects.…”