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Simvastatin attenuates the activity of matrix metalloprotease-9 in aneurysmal aortic tissue
J Evans1, J T Powell, E Schwalbe
1Department of Surgery, University Hospitals of Leicester, UK. jev2@hotmail.com
Abstract:
To investigate whether statins reduce the concentration of MMP-9 in the aortic wall, we randomised patients undergoing elective open repair of an abdominal aortic aneurysm (AAA) to a pre-operative course of either simvastatin or placebo. MMPs in aortic biopsies were measured using gelatin zymography. Although recruitment closed early because of increasing statin use among eligible patients, with only 21 patients we demonstrated a 40% reduction in MMP-9 levels in the AAA wall in patients randomised to simvastatin. This provides a possible molecular mechanism to explain the reportedly beneficial effects of statins to slow AAA growth.
Insights
Simvastatin significantly reduced matrix metalloproteinase-9 (MMP-9) in abdominal aortic aneurysm (AAA) walls. This finding suggests a molecular mechanism for statins potentially slowing AAA growth.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Pharmacology
Background:
- Abdominal aortic aneurysm (AAA) is a life-threatening condition.
- Matrix metalloproteinases (MMPs), particularly MMP-9, are implicated in AAA pathogenesis.
- Statins are widely used cholesterol-lowering drugs with potential anti-inflammatory effects.
Purpose of the Study:
- To determine if statins reduce MMP-9 concentration in the aortic wall of patients with AAA.
- To explore a potential molecular mechanism for the beneficial effects of statins in AAA.
Main Methods:
- Randomized controlled trial comparing simvastatin and placebo pre-operatively in AAA patients.
- Aortic biopsies were collected during elective open AAA repair.
- Matrix metalloproteinase (MMP) levels, specifically MMP-9, were quantified using gelatin zymography.
Main Results:
- A 40% reduction in MMP-9 levels was observed in the AAA wall of patients treated with simvastatin.
- Recruitment was limited due to widespread statin use among eligible patients, resulting in a small sample size (n=21).
Conclusions:
- Pre-operative simvastatin administration significantly reduces MMP-9 levels in the abdominal aortic aneurysm wall.
- This study provides a potential molecular explanation for the observed benefits of statins in slowing AAA progression.
