Uptake of tetracycline by aortic aneurysm wall and its effect on inflammation and proteolysis

Background: Proteolytic degradation of the aortic wall by matrix metallopro teinases (MMPs) is considered important in the pathogenesis of abdominal ao rtic aneurysms (AAAs). Many of these MMPs are inhibited by tetracycline der ivatives, which may have the potential to retard aneurysm growth. Methods: Patients undergoing elective repair of an AAA (n = 5) received an intravenous bolus of tetracycline (500mg) on induction of anaesthesia and l evels of tetracycline in serum, aneurysm wall and mural thrombus were asses sed by microbiological assay. In a separate series of patients (n = 7) aneu rysm biopsies were placed into explant culture (with and without tetracycli ne) and the accumulation of protein, hydroxyproline, MMP-9, interleukin (IL ) 6 and monocyte chemoattractant protein (MCP) 1 in the medium was assessed by colorimetric assay or immunoassay. Results: At aortic cross-clamping the median concentration of tetracycline was 8.3 mu g/ml in serum, 2.9 mu g per g tissue in aortic wall and zero in mural thrombus. Tetracycline inhibited, in a concentration-dependent manner , both MMP-9 and MCP-1 secretion (P=0.022 and P=0.018 respectively), but di d not alter hydroxyproline or IL-6 secretion. At the highest concentration of tetracycline (100 mu g/ml) median MMP-9 secretion was reduced from 27 to 5 ng/ml (P= 0.007) and median MCP-1 secretion was reduced from 50 to 10 ng /ml (P=0.008). Conclusion: Tetracycline rapidly penetrates the aortic wall, but the concen tration achieved may be insufficient to alter collagen turnover through lim itation of MMP production or activity.