Global Gene Expression Profiling of Endothelium Exposed to Heme Reveals an Organ-Specific Induction of Cytoprotective Enzymes in Sickle Cell Disease
2011

Gene Expression Profiling in Sickle Cell Disease

Sample size: 6 publication 10 minutes Evidence: moderate

Author Information

Author(s): Samit Ghosh, Fang Tan, Tianwei Yu, Yuhua Li, Olufolake Adisa, Mario Mosunjac, Solomon F. Ofori-Acquah

Primary Institution: Emory University School of Medicine

Hypothesis

Transcriptional profiling of endothelial cells exposed to heme will reveal the endothelium's capacity to neutralize heme and identify cytoprotective enzymes in sickle cell disease.

Conclusion

Different organ systems in sickle cell disease induce unique profiles of cytoprotective enzymes to neutralize heme.

Supporting Evidence

  • The study identified 51 genes uniquely induced in either pulmonary artery endothelial cells or pulmonary microvascular endothelial cells.
  • Induction of HO-1 and NQO1 was confirmed in post-mortem lung tissues of sickle cell disease patients.
  • The expression of HO-1 was significantly higher in the kidneys and liver of sickle cell disease mice compared to controls.

Takeaway

This study found that different organs in sickle cell disease patients have different ways of protecting themselves from damage caused by heme.

Methodology

Total RNA was isolated from heme-treated endothelial cells and analyzed using microarray technology to identify differentially expressed genes.

Potential Biases

Potential bias in the interpretation of results due to the limited number of human samples analyzed.

Limitations

The study did not examine the expression of other Nrf2-regulated genes and focused only on HO-1 and NQO1.

Participant Demographics

The study involved transgenic mice and post-mortem lung tissues from sickle cell disease patients.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0018399

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