Both
aortic aneurysm and dissection are life threatening pathologies. In the lack of a conservative medical treatment, the only
therapy consists of modifying cardiovascular risk factors and either surgical or endovascular treatment. Like many other
cardiovascular diseases, in particular
atherosclerosis,
aortic aneurysm and dissection have a strong inflammatory phenotype.
Inflammasomes are part of the innate immune system. Upon stimulation they form multi
protein complexes resulting mainly in activation of interleukin-1β and other
cytokines. Considering the gathering evidence, that
inflammasomes are decisively involved in the emergence and progression of
aortic diseases,
inflammasome targeted
therapy provides a promising new treatment approach. A systematic review following the
PRISMA guidelines on the current preclinical data regarding the potential role of
inflammasome targeted
drug therapy as novel treatment option for
aortic aneurysms and dissections was performed. Included were all rodent models of
aortic disease (
aortic aneurysm and dissection) evaluating a
drug therapy with direct or indirect inhibition of
inflammasomes and a suitable control group with the use of the same aortic model without the
inflammasome targeted
therapy. Primary and secondary outcomes were incidence of
aortic disease,
aortic rupture, aortic related death, and the maximum aortic diameter. The literature search of MEDLINE (via PubMed), the Web of Science, EMBASE and the Cochrane Central Registry of Registered Trials (CENTRAL) resulted in 8,137 hits. Of these, four studies met the inclusion criteria and were therefore eligible for data analysis. In all of them, targeting of the NOD-, LRR- and pyrin domain-containing
protein 3 (NLRP3)
inflammasome effectively reduced the incidence of
aortic disease and
aortic rupture, and additionally reduced destruction of the aortic wall. Treatment strategies aiming at other
inflammasomes could not be identified. In conclusion,
inflammasome targeted
therapies, more precisely targeting the NLRP3
inflammasome, have shown promising results in rodent models and deserve further investigation in preclinical research to potentially translate them into clinical research for the treatment of human patients with
aortic disease. Regarding other
inflammasomes, more preclinical research is needed to investigate their role in the pathophysiology of
aortic disease. Protocol Registration: PROSPERO 2021 CRD42021279893, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021279893.