Ciprofloxacin enhances matrix metalloproteinases activity in human aortic smooth muscle cells

Background/significance: The fluoroquinolone antibiotics have been associated with disruption of collagen tissue structures (tendon, corneal, and retina) through promotion of the expression of matrix metalloproteinases (MMPs), which promote degradation of collagen fibril. It is possible that fluoroquinolones may increase MMP activity and tissue destruction in other organs including aorta. Increased production and activity of MMPs and subsequent breaking down of collagen/elastin fibers in aortic wall plays an important role in abdominal aortic aneurysm (AAA) formation. However, no study has been done to evaluate the effect of fluoroquinolone on MMP activity in aortic tissue. Purpose: We hypothesize that fluoroquinolone may induce the formation and deterioration of aortic aneurysm through promoting MMP activity and collagen degradation. Since aortic smooth muscle cells are the major source of MMPs in aortic wall, we assessed the effect of fluoruinolone on MMP activities in human aortic smooth muscle cells. Methods: Cultured passage 3 human aortic smooth muscle cells were subjected to total 48hrs treatment of Ciprofloxacin (5ng/ml, 50ng/ml) or control culture media. After the treatment, culture media was collected and total MMP activities were assessed by Zymograph (10% Gelatin gel). Results: In cultured human aortic smooth muscle cells, Ciprofloxacin 5ng/ml significantly increased total MMP activity by 2.2 folds (n=4, pConclusion: Ciprofloxacin (5ng/ml and 50ng/ml) significantly increased total MMP activity in cultured human aortic smooth muscle. 5ng/ml is also the therapeutic concentration of Ciprofloxacin in human tissue. Our result indicated that use of fluoroquinolone antibiotics may induce proteolytic degradation of collagen structure through promoting MMP activity in aortic wall. Given the extremely broad use of fluoroquinolone and devastating outcome of AAA, it is important to assess the possible risk of aneurysm promoting effect of these antibiotics to guide antibiotic treatments.