Abstract
Human exposure to environmental arsenic induces cardiovascular diseases such as arrhythmias, hypertension, and arteriosclerosis. Here, we review the toxicological and cardiovascular impacts of arsenic in in vitro cardiac and vascular models. The mechanism of arsenic-induced cardiovascular impairments includes oxidative stress, epigenetic modifications, chromatin instability, subcellular damage, and premature aging. The different types of cardiac and vascular cells exhibit distinct responses to arsenic exposure. Arsenic causes arrhythmias, which involve alteration of cardiomyocyte potassium channels and, in turn, repolarization issues. This is mainly due to redox signals that cause epigenetic modifications of potassium channels. On the other hand, vascular lesions, such as damage to blood vessels, occur mainly due to an imbalance in redox levels. This imbalance leads to premature senescence of cells and stop the cell cycle. Furthermore, intracellular accumulation of calcium and ferrous ions plays a major role in arsenic-induced vascular cell apoptosis and cardiomyocyte ferroptosis, respectively.
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Abbreviations
- AT1R:
-
Angiotensin II type I receptor
- As3MT:
-
Arsenite methyltransferase
- CDC2:
-
Cell division control 2
- DSBs:
-
DNA double-strand breaks
- FasL:
-
Factor-associated suicide ligand
- hERG:
-
Human ether-a-go-go-related gene
- HUVECs:
-
Human umbilical vein endothelial cells
- IK1 :
-
Inward rectifier potassium current
- MMAIII :
-
Monomethylarsonous acid
- Nrf2:
-
Nuclear factor erythroid-2-related factor 2
- KCNJ2:
-
Potassium inwardly rectifying channel subfamily J member 2
- KCNE1:
-
Potassium voltage-gated channel subfamily E regulatory subunit 1
- KCNH2:
-
Potassium voltage-gated channel subfamily H member 2
- KCNQ1:
-
Potassium voltage-gated channel subfamily Q member 1
- IKr :
-
Rapidly activating delayed rectifier potassium current
- ROS:
-
Reactive oxygen species
- NADPH:
-
Reduced nicotinamide adenine dinucleotide phosphate
- SA-β-Gal:
-
Senescence β-galactosidase
- IKs :
-
Slowly activating delayed rectifying potassium current
- VECs:
-
Vascular endothelial cells
- VSMCs:
-
Vascular smooth muscle cells
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This work was supported by the National Natural Science Foundation of China (grant number 82103883), Research Fund of Anhui Institute of Translational Medicine (2022zhyx-C15), and Scientific Research Fund from Anhui Medical University (2021xkj010).
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Wāng, Y., Ma, L., Wang, C. et al. Cardiovascular adverse effects and mechanistic insights of arsenic exposure: a review. Environ Chem Lett 22, 1437–1472 (2024). https://doi.org/10.1007/s10311-023-01677-0
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DOI: https://doi.org/10.1007/s10311-023-01677-0