Suppression of Apoptosis by Nitric Oxide via Inhibition of Interleukin-1β–converting Enzyme (ICE)-like and Cysteine Protease Protein (CPP)-32–like Proteases
Key result
Shear stress completely abrogated TNF-alpha-mediated increase in DNA-fragmentation (57% vs 446%, P<0.05) via nitric oxide-mediated inhibition of ICE/CPP-32-like proteases.
Why the study?
Does shear stress and nitric oxide suppress TNF-alpha-induced apoptosis in human endothelial cells?
Population
Human umbilical venous endothelial cells treated with tumor necrosis factor-alpha to induce apoptosis
Comparison
Shear stress and/or exogenous nitric oxide donors vs Static conditions or absence of NO donors
Design
Preclinical
Authors
Discussion
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Member takes
Implication
Hypothesis-generating in animal models; leaves open translation to human endothelial protection and atherosclerosis.
Structured PICO
Does shear stress and nitric oxide suppress TNF-alpha-induced apoptosis in human endothelial cells?
P
Population
Human umbilical venous endothelial cells (HUVEC) treated with tumor necrosis factor-alpha (TNF-alpha) to induce apoptosis
I
Intervention
Shear stress (15 dynes/cm2) and/or exogenous nitric oxide (NO) donors
C
Comparator
Static conditions or absence of NO donors
O
Outcome
Apoptosis quantified by ELISA specific for histone-associated DNA-fragments and internucleosomal DNA-fragmentationsurrogate
Main Result
Absolute Event Rate: 57% vs 446%
p-value: p=<0.05
Shear stress-mediated nitric oxide formation protects endothelial cells from TNF-alpha-induced apoptosis by inhibiting ICE/CPP-32-like proteases via S-nitrosylation, potentially contributing to endothelial integrity and atheroprotection.
Cite This Study
Dimmeler et al. (1997) studied Endothelial cell apoptosis. Shear stress and Nitric Oxide vs. TNF-alpha alone was evaluated on TNF-alpha-induced apoptosis (DNA-fragmentation) (p=<0.05). Shear stress completely abrogated TNF-alpha-mediated increase in DNA-fragmentation (57% vs 446%, P<0.05) via nitric oxide-mediated inhibition of ICE/CPP-32-like proteases.