title: Matrix metalloproteinases in the aneurysm wall of patients treated with low-dose doxycycline.
abstract: The purpose of this study was to determine the effect of low-dose doxycycline on matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP)-1 expression in the wall of abdominal aortic aneurysms. A double-blind, randomized study was conducted of patients treated with doxycycline (100 mg/d orally) or placebo for 1 month prior to surgery. MMP-2, -3, and -9 (zymogen and activity); MMP-1, -2, -3, -7, -9, -11, -12, and -14; and TIMP-1 (messenger ribonucleic acid [mRNA]) were measured in the aneurysm wall. No differences were found between the treatment and placebo groups in zymogen levels of MMP-2, -3, or -9 or in the free or total activities of MMP-2 and -9. Treatment with doxycycline also had no effect on the concentration of any mRNA measured. No relationship was found between the number of tablets taken and MMP or TIMP protein, mRNA, or activity levels in the aneurysm wall. Low-dose doxycycline treatment does not alter the expression or activity of metalloproteinases or their inhibitor, TIMP-1, in the aneurysm wall.
authors.affiliation: Academic Department of Surgery, King's College, St Thomas' Campus, London, UK.
authors.forename: Ren
authors.initials: R
authors.lastname: Ding
authors.forename: Cathy L
authors.initials: CL
authors.lastname: McGuinness
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Burnand
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sullivan
authors.forename: Alberto
authors.initials: A
authors.lastname: Smith
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000201:enzymology; D017544:Aortic Aneurysm, Abdominal / Q000201:enzymology*; D004311:Double-Blind Method; D004318:Doxycycline / Q000494:pharmacology*; D004792:Enzyme Precursors / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D020782:Matrix Metalloproteinases / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis
chemical_list: D000900:Anti-Bacterial Agents; D004792:Enzyme Precursors; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004318:Doxycycline