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Intracellular Ca2+ homeostatic regulation and 4-hydroxynonenal-induced aortic endothelial dysfunction.
Elizabeth J McConnell1, Beat U Raess
1Department of Pharmacology and Toxicology, Indiana University School of Medicine, Evansville, IN 47712, USA.
Endothelium : Journal of Endothelial Cell Research
|August 7, 2003
Summary
The lipid peroxidation product 4-hydroxynonenal (HNE) significantly increases intracellular calcium in endothelial cells, leading to cell damage. This suggests HNE-induced disturbances in calcium homeostasis contribute to its atherogenic effects.
Area of Science:
- Biochemistry
- Cell Biology
- Cardiovascular Research
Background:
- 4-hydroxynonenal (HNE) is a lipid peroxidation product known to affect erythrocyte calcium transport.
- HNE is implicated in cellular damage and may play a role in atherosclerosis.
Purpose of the Study:
- To investigate the effects of HNE on passive and active calcium (Ca2+) transport in endothelial cells.
- To characterize Ca2+ uptake and efflux mechanisms in cultured porcine aortic endothelial cells (PAEC).
Main Methods:
- Utilized 45Ca2+ to measure Ca2+ uptake and efflux in PAEC.
- Assessed the impact of HNE on Ca2+ accumulation and cellular morphology.
- Investigated the effects of various inhibitors and ionophores on Ca2+ transport.
Main Results:
- HNE dose-dependently and time-dependently increased total 45Ca2+ accumulation in PAEC by up to 562% (EC50 = 64.0 µM).
- Observed morphological changes in PAEC, including vacuolization, nuclear swelling, and cell detachment, preceding significant Ca2+ accumulation changes.
- Demonstrated that HNE disrupts Ca2+ homeostasis in vascular endothelium.
Conclusions:
- HNE significantly elevates intracellular Ca2+ levels in endothelial cells.
- HNE-induced disruption of Ca2+ homeostasis likely contributes to its cytotoxic effects and atherogenic potential.