Uptake of tetracycline by aortic aneurysm wall and its effect on inflammation and proteolysis.
BACKGROUND
Proteolytic degradation of the aortic wall by matrix metalloproteinases (MMPs) is considered important in the pathogenesis of abdominal aortic aneurysms (AAAs). Many of these MMPs are inhibited by tetracycline derivatives, 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 (500 mg) on induction of anaesthesia and levels of tetracycline in serum, aneurysm wall and mural thrombus were assessed by microbiological assay. In a separate series of patients (n = 7) aneurysm biopsies were placed into explant culture (with and without tetracyline) 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 microg/ml in serum, 2.9 microg 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 did not alter hydroxyproline or IL-6 secretion. At the highest concentration of tetracycline (100 microg/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).


CONCLUSIONS
Tetracycline rapidly penetrates the aortic wall, but the concentration achieved may be insufficient to alter collagen turnover through limitation of MMP production or activity.
Franklin
I J
IJ
Department of Vascular Surgery, Imperial College School of Medicine at Charing Cross, Charing Cross Hospital, London, UK.
Harley
S L
SL
Greenhalgh
R M
RM
Powell
J T
JT
D017544:Aortic Aneurysm, Abdominal / Q000209:etiology / Q000378:metabolism*; D001025:Aortitis / Q000209:etiology; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D020780:Matrix Metalloproteinase 9; D061965:Matrix Metalloproteinase Inhibitors; D011500:Protein Synthesis Inhibitors / Q000493:pharmacokinetics*; D013752:Tetracycline / Q000493:pharmacokinetics*
D018932:Chemokine CCL2; D061965:Matrix Metalloproteinase Inhibitors; D011500:Protein Synthesis Inhibitors; D003094:Collagen; D020780:Matrix Metalloproteinase 9; D013752:Tetracycline