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Infectious and inflammatory stimuli decrease endothelial nitric oxide synthase activity in vitro.
Simona Cardaropoli1, Francesca Silvagno, Emanuella Morra
1Department of Genetics, Biology and Biochemistry, University of Turin, Via Santena 5bis, Turin, Italy.
Journal of Hypertension
|November 5, 2003
Summary
Inflammation and infection reduce endothelial nitric oxide synthase (eNOS) expression, impacting blood pressure regulation. Iron deficiency further exacerbates this effect, linking infection to hypertension.
Area of Science:
- Vascular Biology
- Iron Metabolism
- Hypertension Research
Background:
- Iron metabolism perturbations, particularly elevated serum ferritin, are linked to inflammation and hypertension.
- Endothelial nitric oxide synthase (eNOS), crucial for vascular tone, is regulated by heme-dependent dimerization and iron availability.
Purpose of the Study:
- To investigate the regulation of anti-hypertensive eNOS in human endothelial cells.
- To correlate eNOS regulation with iron metabolism alterations and in vivo stimuli like inflammation and infection.
Main Methods:
- Human endothelial cells treated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNFalpha), succinylacetone, and desferrioxamine.
- eNOS expression and activation assessed via SDS-PAGE (monomer vs. dimer) and RT-PCR for mRNA.
- Ferritin content evaluated.
Main Results:
- LPS and TNFalpha reduced eNOS monomer and dimer expression, with mRNA down-regulation.
- Iron deficiency (succinylacetone, desferrioxamine) affected protein levels but not mRNA transcription.
- Endothelial cells were not found to be the source of increased ferritin.
Conclusions:
- Infectious and inflammatory stimuli down-regulate eNOS expression at mRNA and protein levels.
- Heme and iron shortage enhance this down-regulation.
- eNOS may represent a molecular link between infection and hypertension.