Researchers have discovered that the expression of bradykinin receptor 1 may play an important role in the pathomechanism of hereditary angioedema, according to a study published in the International Journal of Molecular Sciences.
Hereditary angioedema is driven by a lack of C1-inhibitor protein, which is caused by mutations in the SERPING1 gene.
“C1-inhibitor deficiency causes a broad spectrum of homeostasis dysregulation in a plasma bradykinin-forming cascade triggering overproduction of bradykinin due to uninhibited effects of activated factor XII (FXII) and plasma kallikrein,” the authors of the study wrote.
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This disease is characterized by recurrent episodes of edema attacks. The most commonly affected areas are the skin, upper airways, genitals, and gastrointestinal tract.
Bradykinin causes vascular permeability via the activation of 2 receptors: bradykinin receptor 1 and bradykinin receptor 2. While bradykinin receptor 2 is understood to play a major role in the symptomatology of hereditary angioedema, the role of bradykinin receptor 1 is less clear. The authors of the study hence decided to investigate if bradykinin receptor 1 has any role in the pathomechanism of hereditary angioedema. To do so, the research team recruited 70 participants: 40 with hereditary angioedema and 30 healthy individuals.
Read more about hereditary angioedema etiology
“The level of bradykinin receptors was determined in populations of CD3+, CD4+, CD8+, and CD14++CD16−, CD14++CD16+ monocytes,” the authors of the study wrote. “In addition, the level of disease activity-specific markers was measured.”
The authors of the study discovered that bradykinin receptor 1 was upregulated in patients with hereditary angioedema during an attack; conversely, the level of its expression was similar in patients with hereditary angioedema who did not experience an attack and the controls. In addition, the researchers reported that bradykinin receptor 2 was overexpressed during edema attacks.
“In conclusion, the results of the research indicate that dynamics in bradykinin receptor expression can be one of the missing players in understanding the [hereditary angioedema] mechanism,” the authors of the study wrote.
Reference
Dyga W, Obtulowicz A, Mikolajczyk T, Bogdali A, Dubiela P, Obtulowicz K. The role of bradykinin receptors in hereditary angioedema due to C1-inhibitor deficiency. Int J Mol Sci. 2022;23(18):10332. doi:10.3390/ijms231810332
