Researchers discovered that protease-activated receptor 1 (PAR1) may play an important role in edema formation in hereditary angioedema (HAE), according to a study published in Allergy, Asthma & Clinical Immunology.

HAE is a disease characterized by recurrent and self-limiting episodes of edema. Edema attacks can sometimes involve the airways, leading to breathing difficulties. HAE is caused by C1 esterase inhibitor deficiency and is an exceedingly rare disease, with an estimated prevalence between 1:10,000 to 1:50,000.

Edema in HAE is caused by the uncontrolled hyperpermeability of capillary endothelial cells as a result of an abnormal release of bradykinin. Endothelial cell dysfunction and other circumstances preceding an edematous attack are not well understood.


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“Although the pathophysiology of HAE attacks are extensively investigated assessing plasma samples, only limited data are available on the ultrastructure and molecular pathomechanism within the affected tissues,” the authors said.

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The researchers hence decided to study the pathomechanisms in HAE caused by C1 esterase inhibitor deficiency. They collected laryngeal tissue from a patient who passed away from an HAE attack that caused suffocation from upper airway edema. They also collected laryngeal tissue from a deceased control patient and analyzed the tissue samples obtained.

“Our most important and novel observation was that the PAR1 expression was strongly reduced in the [C1 esterase inhibitor deficiency HAE] patient compared to the control patient,” the authors said.

The lower expression of PAR1 in the patient with HAE is possibly a reflection of receptor consumption due to PAR1 activation. Previous studies have demonstrated that PAR1 activation can cause hyperpermeability in endothelial cells. This means that PAR1 can become a therapeutic target in future research for the treatment of acute attacks of HAE. 

Reference

Farkas H, Máj C, Kenessey I, et al. A novel pathogenetic factor of laryngeal attack in hereditary angioedema? Involvement of protease activated receptor 1Allergy Asthma Clin Immunol. Published online July 4, 2022. doi:10.1186/s13223-022-00699-7