Doxycycline inhibits elastin degradation and reduces metalloproteinase activity in a model of aneurysmal disease

J Vasc Surg. 1998 Feb;27(2):354-61. doi: 10.1016/s0741-5214(98)70367-2.


Purpose: Abdominal aortic aneurysms are characterized by degradation of the extracellular matrix, with a reduction in the elastin concentration of the arterial media. These changes are mediated by increased levels of endogenous metalloproteinases (MMPs) within the aorta, which provide a potential therapeutic target for pharmacologic agents aimed at reducing the growth rate of small aneurysms. In this study, the ability of doxycycline--an MMP inhibitor--to reduce matrix degradation was assessed in a previously described model of aneurysmal disease that used a brief pulse of elastase to induce MMP production and elastin degradation in arterial organ cultures.

Methods: Porcine aortic segments (n = 8) were preincubated in exogenous pancreatic elastase for 24 hours before culture in standard conditions for 13 days with both 1 and 10 mg/L doxycycline. Control segments were cultured both without doxycycline and without elastase. At the termination of culture, MMPs were extracted from the tissue and quantified by a combination of substrate gel enzymography and immunoblotting. The volume fractions of elastin and collagen were determined by stereologic analysis of sections stained with Miller's elastin and van Gieson's stain.

Results: Stereologic analysis demonstrated a significant preservation of elastin in aorta treated with doxycycline 10 mg/L (p < 0.001) and demonstrated that this preservation was accompanied by a significant reduction in MMP-9 activity (p < 0.02). Immunoblotting for tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) showed no decreased production in the doxycycline-treated groups.

Conclusions: Therapeutic ranges of doxycycline significantly inhibited elastin degradation and MMP-9 production within aortic organ cultures. These data suggest that doxycycline may have a potential application in reducing the growth rates of small abdominal aortic aneurysms.

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aortic Aneurysm, Thoracic / drug therapy*
  • Aortic Aneurysm, Thoracic / pathology
  • Doxycycline / pharmacology*
  • Elastin / drug effects*
  • Enzyme Inhibitors / pharmacology*
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase Inhibitors*
  • Metalloendopeptidases / antagonists & inhibitors*
  • Organ Culture Techniques
  • Swine


  • Enzyme Inhibitors
  • Matrix Metalloproteinase Inhibitors
  • Elastin
  • Metalloendopeptidases
  • Matrix Metalloproteinase 9
  • Doxycycline