The role of doxycycline in reducing MMP-9 and acute-phase reactants to limit abdominal aortic aneurysm growth: A systematic review

Abstract

Background

Abdominal aortic aneurysms (AAAs) are a significant vascular disease characterized by the degradation of medial elastic lamellae, neovascularization, and inflammatory responses. While surgical intervention remains the standard treatment for large or rapidly expanding AAAs, there is no universally accepted pharmacological therapy to prevent aneurysm progression. Matrix metalloproteinases (MMPs), particularly MMP-9, and inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) are implicated in AAA pathogenesis, making them potential therapeutic targets. Doxycycline, a broad-spectrum tetracycline antibiotic, has demonstrated inhibitory effects on MMP-9 and anti-inflammatory properties. However, its efficacy in slowing AAA progression remains unclear.

Methods

A systematic review was conducted following PRISMA guidelines. Electronic searches were performed in PubMed, MEDLINE, EMBASE, and ClinicalTrials.gov. Inclusion criteria encompassed randomized controlled trials (RCTs), cohort studies, in vitro studies, and systematic reviews evaluating the effects of doxycycline on AAA growth. Data extraction was performed using Covidence software, and study quality was assessed using the Cochrane Risk of Bias Tool 2.0 (RoB2) for RCTs, the QUIN tool for in vitro studies, and the SYRCLE tool for animal experiments. Statistical analysis employed a random-effects model to evaluate heterogeneity among studies.

Results

The initial search identified 1313 references, of which 10 studies met inclusion criteria: two RCTs, two systematic reviews, three in vitro studies, one in vivo study, one methodological study, and one experimental study. The two RCTs, involving 515 patients with an average age of 71 years, reported minimal to no significant reductions in AAA growth following doxycycline administration. In contrast, in vitro and in vivo studies demonstrated inhibition of MMP-9 and inflammatory markers, supporting doxycycline’s potential therapeutic role. Meta-analysis was not performed due to high heterogeneity (I² = 75%). Risk of bias assessment indicated a low risk for RCTs, whereas in vitro and in vivo studies showed a moderate risk of bias.

Conclusion

While doxycycline exhibits promising biochemical effects in AAA pathophysiology, its clinical efficacy remains uncertain. Current evidence does not support its routine use in AAA management outside clinical trials. Future research should focus on targeted pharmacotherapy integrating patient-specific biomarkers to enhance therapeutic outcomes.