Novel Insights Into the Critical Role of Bradykinin and the Kinin B2 Receptor for Vascular Recruitment of Circulating Endothelial Repair–Promoting Mononuclear Cell Subsets

Abstract

hi monocytes, from CAD patients as compared with healthy subjects. B2R stimulation induced CD18 activation in early outgrowth cells of healthy subjects, but not in early outgrowth cells of CAD patients. Adenoviral B2R overexpression enhanced in vivo vascular recruitment and rescued impaired endothelial repair capacity of early outgrowth cells from CAD patients. Conclusions-We newly report that bradykinin/B2R signaling may promote endothelial repair after arterial injury by selective recruitment and functional activation of B2R-expressing circulating mononuclear cell subsets. In CAD patients, B2R downregulation on endothelial repair-promoting circulating mononuclear cells substantially impairs the bradykinindependent endothelial repair, representing a novel mechanism promoting endothelial injury in CAD patients. (Circulation. 2013;127:594-603.)

Novel Role of Kallistatin in Vascular Repair by Promoting Mobility, Viability, and Function of Endothelial Progenitor Cells

“…In the current study, we demonstrated that kallistatin reduces vascular injury by enhancing EPC mobility and functional capacity. Likewise, tissue kallikrein‐kinin and kinin B2 receptor signaling have also been observed to promote cardiac neovascularization by enhancing EPC migration and function . Consequently, kallistatin has a unique protective role in endothelial injury, independent of its interaction with tissue kallikrein.…”

“…Likewise, tissue kallikrein-kinin and kinin B2 receptor signaling have also been observed to promote cardiac neovascularization by enhancing EPC migration and function. [52][53][54][55] Consequently, kallistatin has a unique protective role in endothelial injury, independent of its interaction with tissue kallikrein.…”

Long‐term safety of icatibant treatment of patients with angioedema in real‐world clinical practice

“…Serious adverse events occurred infrequently, and none were cardiovascular‐related. Studies have shown that bradykinin B2 receptor blockade might impair endothelial repair after an acute cardiovascular event . However, icatibant has a short half‐life and the effect of intermittent treatments is likely transient.…”

“…The Icatibant Outcome Survey (IOS; NCT01034969) is an ongoing, international, prospective, observational registry monitoring efficacy and safety of icatibant in the real‐world setting. Preclinical studies have suggested that icatibant‐associated adverse events (AEs) may relate to its mechanism of action . The current analysis evaluated incidence of cardiovascular‐related AEs, as well as other common AEs in icatibant‐treated patients.…”

The safety of treatments for angioedema with hereditary C1 inhibitor deficiency

“…Interestingly, Kränkel et al reported that in patients with coronary artery disease there is a substantial impairment of the bradykinin/bradykinin-B2-receptor (B2R) signalingdependent endothelial repair, which usually acts by selective recruitment and functional activation of B2R-expressing circulating mononuclear cell subsets. Therefore, inhibition of bradykinin activity with icatibant might further worsen the repair mechanism [44]. Although there is evidence supporting a positive effect of bradykinin antagonism immediately following a stroke [45,46], icatibant should also be administered carefully in patients after ischemic cerebral events, since it may attenuate the beneficial late phase of the neuroprotective effects of bradykinin [47,48].…”