Matrix metalloproteinases in the aneurysm wall of patients treated with low-dose doxycycline

Ren Ding1, Cathy L McGuinness, Kevin G Burnand

  • 1Academic Department of Surgery, King's College, St Thomas' Campus, London, UK.

Vascular
|November 18, 2005
PubMed

Insights

Low-dose doxycycline did not alter matrix metalloproteinase (MMP) or tissue inhibitor of metalloproteinase (TIMP)-1 levels in abdominal aortic aneurysms. This study found no significant changes in MMP or TIMP-1 expression or activity with doxycycline treatment.

Area of Science:

  • Cardiovascular Research
  • Biochemistry
  • Pharmacology

Background:

  • Abdominal aortic aneurysms (AAAs) are characterized by the degradation of the extracellular matrix, involving matrix metalloproteinases (MMPs) and their inhibitors, such as tissue inhibitor of metalloproteinase-1 (TIMP-1).
  • Doxycycline, a matrix metalloproteinase inhibitor, has been investigated for its potential therapeutic effects in AAA disease.

Purpose of the Study:

  • To investigate the impact of low-dose doxycycline on the expression and activity of various matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the walls of abdominal aortic aneurysms.
  • To assess whether doxycycline treatment influences MMP and TIMP-1 at the protein and messenger RNA (mRNA) levels.

Main Methods:

  • A double-blind, randomized study involving patients undergoing surgery for abdominal aortic aneurysms.
  • Patients received either 100 mg/d of doxycycline orally or a placebo for one month prior to surgery.
  • Analysis of MMP-2, -3, and -9 (zymogen and activity), other MMPs (MMP-1, -2, -3, -7, -9, -11, -12, -14), and TIMP-1 mRNA in the aneurysm wall tissue.

Main Results:

  • No significant differences were observed between the doxycycline and placebo groups in the zymogen levels of MMP-2, -3, or -9.
  • Free and total activities of MMP-2 and MMP-9 did not differ between the treatment and placebo groups.
  • Doxycycline treatment had no discernible effect on the concentration of any measured MMP or TIMP-1 mRNA, nor was any relationship found between adherence to treatment and MMP/TIMP levels.

Conclusions:

  • Low-dose doxycycline (100 mg/d) does not alter the expression or activity of matrix metalloproteinases or tissue inhibitor of metalloproteinase-1 in the aneurysm wall.
  • These findings suggest that this regimen of doxycycline is unlikely to modify the key molecular pathways involved in abdominal aortic aneurysm pathogenesis.
  • Further research may be needed to explore alternative dosing strategies or different therapeutic agents for managing abdominal aortic aneurysms.

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