The activation of the cannabinoid receptor type 2 reduces neutrophilic protease-mediated vulnerability in atherosclerotic plaques

Abstract

Cannabinoid receptor type 2 receptor is down-regulated in unstable human carotid plaques. Since CB(2) activation prevents neutrophil release of MMP-9 in vivo and in vitro, this treatment strategy might selectively reduce carotid vulnerability in humans.

Treatment with Evasin-3 Reduces Atherosclerotic Vulnerability for Ischemic Stroke, but Not Brain Injury in Mice

“…Taking together, these results indicate that in vivo systemic CXC chemokine inhibition with the selective CXC chemokine-binding protein Evasin-3 was associated with a weak improvement of neutrophilic intraplaque inflammation potentially associated with mouse plaque vulnerability. 18 Treatment with Evasin-3 Does Not Affect CXC Chemokine Levels and Cerebral Injury in a Mouse Model of Cerebral Transient Focal Ischemia/Reperfusion Evasin-3 has been shown to mainly inhibit CXC chemokine bioactivity rather than tissue and serum levels. 8,9 In the stroke model, the bioactivity of each Evasin-3 batch was verified in vitro using mouse neutrophil chemotaxis assay before use (data not shown).…”

“…18 Sections and aortas were counterstained with Mayer's hemalun and rinsed in distilled water. Quantifications were performed using the MetaMorph software.…”

“…18,22 The fold change of mRNA levels was calculated by the comparative C t method. The measured C t values were first normalized to the Hprt internal control, by calculating a delta C t (DC t ).…”

“…No effect on macrophage (CD68 þ cell) recruitment was shown in the different treatment groups as compared with control Vehicle or sham-operated mice ( Figure 5C), indicating that selective inhibition of CXC chemokine bioactivity mainly affect neutrophil recruitment within inflamed or infarcted peripheral tissues. 8,9 The production of some neutrophilic products (such as MMP-9, MMP-8, Neutrophil elastase, and myeloperoxidase, previously shown to increase brain and cardiovascular injuries) 10,18 within the infarcted brain hemispheres was also investigated. Evasin-3 treatment failed to significantly reduce pro-MMP-9 serum levels as compared with control Vehicle at 24 hours of reperfusion ( Figure 6A).…”

“…This effect was observed in both aortic root and carotid atherosclerotic plaques, previously shown as characterized by different degree profiles of vulnerability. 12 Since this neutrophilic protease has been described to induce a 'cannibal' digestion of protective collagen products within atherosclerotic plaques, 18 we also considered the potential effects of Evasin-3 treatment on intraplaque collagen. Despite a weak effect, we observed a significant increase in collagen deposition in aortic root plaques in Evasin-3-treated mice as compared with controls.…”