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Published on: August 24, 2019
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.
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.
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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