Abstract 1031: First Human Experiments: Aggressive Statin Therapy Reduced Key Inflammatory Factors including c-Jun N-terminal kinase (JNK) and Dendritic Cell and Matrix Metalloproteinase Expression in Human Abdominal Aortic Aneurysmal Wall

Abstract

Abdominal aortic aneurysms (AAA) accumulate feature of a chronic inflammatory disorder and irreversible destruction connective tissue. Recent experimental study demonstrated that c-Jun N terminal kinase (JNK) was a proximal signaling molecule in the pathogenesis of AAA and vascular dendritic cells (DC) were the key molecular in inflammatory reaction and the degradation of the extracellular matrix. Statins can inhibit cell proliferation and vascular inflammation, which might contribute to prevent AAA progrssion. But supporting clinical data from human studies are lacking. We hypothesized that atorvastatin might inhibit JNK and DC, resulting in suppression of inflammatory cells and matrix metalloproteinase (MMPs) in human tissue of AAA. Methods : Patients with AAA were randomized to the atorvastatin (20 mg/day, 10 patients) group or control (10 patients) group. After treatment of 4 weeks, patients underwent abdominal aorta replacement, tissue specimens were obtained, and the tissue composition was assessed with special stains and immunocytochemistry with quantitative image analysis. Results :Atorvastatin significantly reduced JNK and DC expression (46% and 72%) compared to control. T cells, macrophages (60%, 72%, P< 0.05), and MMP-2 and MMP-9 immunoreactivity (47%, 43%, P< 0.05) were also suppressed in atorvastatin group. However, tissue expression of metalloproteinase 1 (TIMP-1) immunoreactivity and a collagen content by sirius red staining were similar in both groups. In atorvastatin group, serum LDL-C level was significantly decreased by 40%. Conclusion: Atorvastatin treatment reduced the JNK expression and DE, resulting in inflammatory cells content and the expression of MMPs in human abdominal aortic aneurysm wall.