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Unfolded Protein Response supports endothelial barrier function

Nektarios Barabutis1

  • 1School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana Monroe, Monroe, LA, 71201, USA.

Biochimie
|August 13, 2019
PubMed

Insights

Heat shock protein 90 (Hsp90) inhibitors and P53 activation protect against inflammation by triggering the Unfolded Protein Response (UPR). This UPR induction is hypothesized to safeguard the vasculature from inflammatory damage.

Area of Science:

  • Cardiovascular Science
  • Cellular Biology
  • Pharmacology

Background:

  • Endothelial barrier dysfunction during inflammation can cause Acute Respiratory Distress Syndrome.
  • Heat shock protein 90 (Hsp90) inhibitors exhibit anti-inflammatory effects in endothelial cells.
  • Recent findings implicate P53 in mediating these anti-inflammatory activities.

Purpose of the Study:

  • To propose that the Unfolded Protein Response (UPR) activation protects the vasculature from inflammatory insults.
  • To link Hsp90 inhibition and P53 induction to UPR activation.

Main Methods:

  • Experimental models of Acute Lung Injury.
  • Investigating the role of Hsp90 inhibitors.
  • Assessing P53 activity and UPR element activation.

Main Results:

  • Hsp90 inhibition and P53 induction are linked to UPR activation.
  • P53 appears to orchestrate anti-inflammatory responses in experimental models.
  • These pathways suggest a protective mechanism against endothelial barrier dysfunction.

Conclusions:

  • UPR induction is a potential protective mechanism for vasculature against inflammation.
  • Hsp90 inhibitors and P53 modulation may represent novel therapeutic strategies.
  • Targeting UPR could mitigate inflammatory lung injury and cardiovascular complications.

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