Elastase inhibitor AZD9668 treatment prevented progression of experimental abdominal aortic aneurysms

Abstract

AZD9668 treatment could therefore constitute a new therapeutic tool for treatment of AAA.

Free DNA precipitates calcium phosphate apatite crystals in the arterial wall in vivo

“…As in humans, experimental aneurysms in rats have been reported to contain calcifications in association with free DNA release 13 . Here we used in vivo CT scan to detect calcifications in elastase-induced experimental aneurysms in rats (Supplemental Fig.…”

“…Aortic samples from rats that underwent intraluminal aortic perfusion of pancreatic elastase, along with, or without, repeated injections of Porphyromonas gingivalis (PG) as previously described 13 , were fixed in 5% paraformaldehyde and embedded in paraffin to obtain 6 µmthick sections for histological analysis.…”

“…The aortic wall of human AAA is highly calcified. We recently published in an experimental model of AAA that repeated injections of weak pathogens increased the aneurysm diameter by increasing the neutrophil content in the intraluminal thrombus 24 , enhancing both the content and release of cell-free DNA and wall calcifications in rat 13 . Thus, here we tested the hypothesis that this increase in calcifications could be linked, at least in part, to the presence of free DNA.…”

Neutrophil elastase inhibitor purification strategy from cowpea seeds

“…Although human neutrophil elastase (HNE) has an active role in many physiological processes in human organism, mainly involving innate immune response, tissue remodeling and inflammation, it is also associated with many disorders when its activity is deregulated [68–71]. According to the literature, HNE is involved with many inflammatory diseases such as COPD, cystic fibrosis, bronchiectasis, pulmonary arterial hypertension, pulmonary fibrosis, acute lung injury [68, 69, 72, 73], atherosclerosis, aortic aneurysm [74–76] and inflammatory renal diseases [77].…”

Neutrophil Elastase Inhibitors and Chronic Kidney Disease

“…In patients with CF, AZD9668 was well tolerated, reduced inflammation and lung injury, as showed by the reduction in IL-6, and in urinary desmosine, respectively; however, it seems to have little impact on NE activity or lung function 77 . Moreover, studies using a rat experimental model reported a beneficial effect for AZD9668 in the treatment abdominal aortic aneurysm, reducing the levels of MPO, NE and cfDNA that contribute to progression of the disease 79 .…”