Endothelin and bradykinin: ‘brothers‐in‐arms’ in Chagas vasculopathies?

Abstract

Reports of Chagas disease are increasing in non-endemic populations across the globe. Apart from vector eradication and prevention efforts by public health organizations, current pharmacological interventions are sparse and show important side effects. In this issue of the BJP, Andrade et al. elegantly demonstrate a new pharmacological paradigm whereby Trypanosoma cruzi host cell invasion requires significant cross-talk between receptors for kinins and endothelins. It is shown, for example, that acting via both ETA and ETB receptors, endothelin-1 (ET-1) cooperates with the (TLR2/CXCR2/B2 kinin receptor) complex to activate inflammatory processes in response to invading trypomastigotes.This study by Andrade et al. prompts, however, several important questions, summarized in this Commentary, such as the putative role of chymase-dependent production of ET-1, the contentious protective role of ACE inhibitors in Chagasic patients, the unexplored role of de novo formed B1 receptors for kinins triggered by cytokines and the putative role of compartmentalized calcium pools in host cell invasion by trypomastigotes. LINKED ARTICLEThis article is a commentary on Andrade et al., pp. 1333-1347 of this issue. To view this paper visit http://dx

Endothelin-1 and its role in the pathogenesis of infectious diseases

“…This mechanism can enhance parasite invasion of cardiovascular cells [188, 189]. TLR2, the B2 kinin and CXCR2 receptors trigger intracellular inflammatory pathways induced by T. cruzi and directly interact with endogenous ET-1 [188, 189].…”

“…This mechanism can enhance parasite invasion of cardiovascular cells [188, 189]. TLR2, the B2 kinin and CXCR2 receptors trigger intracellular inflammatory pathways induced by T. cruzi and directly interact with endogenous ET-1 [188, 189]. Andrade et al demonstrated that HOE-140, a B2 kinin receptor (BK2R) antagonist can reduces the ET-1-induced increase in T. cruzi invasion seen in human smooth muscle cells in vitro [188, 189].…”

“…TLR2, the B2 kinin and CXCR2 receptors trigger intracellular inflammatory pathways induced by T. cruzi and directly interact with endogenous ET-1 [188, 189]. Andrade et al demonstrated that HOE-140, a B2 kinin receptor (BK2R) antagonist can reduces the ET-1-induced increase in T. cruzi invasion seen in human smooth muscle cells in vitro [188, 189]. An interaction between the kinin and endothelin pathways at the early stages of T. cruzi infection has therefore been postulated [188].…”

Kinins and Their Receptors in Infectious Diseases

“…Based on this evidence, D’Orléans-Juste and cols. (2012) raised the importance of investigations about the role of de novo induction of B 1 receptors by cytokines, in Chagas vasculopathies [ 149 ].…”