Carvedilol Protects against Iron-Induced Microparticle Generation and Apoptosis of Endothelial Cells

Abstract

Background: Increased circulating endothelial microparticles (EMPs) have been shown to associate with endothelial dysfunction. We explored the effect of iron on EMP generation by human umbilical vein endothelial cells (HUVECs) and the potential protective effect of carvedilol. Methods: FeCl₃ was added to HUVEC culture. Iron entry into cells was monitored using fluorescent microscopic imaging, while the quantity of EMPs that was released was determined by flow cytometry. The apoptosis of HUVECs was assessed by annexin V/propidium iodide assay and caspase-3 expression. Membrane bleb formation was visualized using electron microscopy. Intracellular production of reactive oxygen species (ROS) was also monitored. The effects of beta-blockers, carvedilol and propranolol on these processes were determined by co-incubation in a dose-dependent manner. Iron entry into HUVECs was not blocked by either beta-blocker. Iron induced the generation of EMPs, the formation of membrane blebs, the apoptosis of HUVECs and the production of ROS, each in a dose-dependent manner. Carvedilol, but not propranolol, ameliorated all of these processes. Results: Our result indicates that iron induces EMP generation and apoptosis of endothelial cells in association with increased oxidative stress. Conclusion: The protective effects of carvedilol, via its antioxidant effect, may have therapeutic potential in patients with iron overload.

Dietary supplement use and nosebleeds in hereditary haemorrhagic telangiectasia ‒ an observational study

“…It may be of concern however, that for five iron users, serum iron concentrations were at least twice the upper limit of normal ( Figure 2B), in keeping with recent data from a healthy volunteers study (5). One in 20 HHT iron users report nosebleeds are worse after iron treatments (5,27), and recent data suggest one plausible biological explanation through activation of endothelial DNA damage response pathways by 10 µM iron (28), an order of magnitude lower than examined in recent iron toxicity studies (29,30).…”

Silica nanoparticles increase human adipose tissue-derived stem cell proliferation through ERK1/2 activation

“…Therefore, it is possible that endocytosis of silica NPs accelerates cell growth whereas cell membrane stress caused by silica MPs induces apoptosis. 35 To further address the mechanism of action of these differentially sized particles, we examined the effects of silica NPs and MPs on the MAPK pathway ( Figure 4A). Involvement of ERK1/2 signaling in cell growth has been reported previously.…”

Endothelial Microparticles and Endothelial Damage: ‘The Tip and the Iceberg'

“…We believe that Gamna-Gandy bodies are the final histopathologic epiphenomenon of cell damage due to iron exposure; conversely, endothelial microparticle generation due to iron exposure may well be the true ‘tip of the iceberg' of the pathophysiology of endothelial damage in all these conditions. The finding by Chan et al [1] might therefore shed further light on the pathophysiology of conditions where free iron compounds are present, such as SCA, thalassaemias and haemochromatosis. Moreover, the finding of a protective action of β-blockers warrants further exploration because of important clinical implications.…”

“…We read with interest the paper by Chan et al [1] from Hong Kong University on the in vitro study and effects of iron on human umbilical vein endothelial cells, which result in endothelial microparticle generation and increased reactive oxygen species production. The same research group also showed that when β-blockers were added, this effect was reduced.…”