Short-term 20-mg atorvastatin therapy reduces key inflammatory factors including c-Jun N-terminal kinase and dendritic cells and matrix metalloproteinase expression in human abdominal aortic aneurysmal wall.
BACKGROUND
Abdominal aortic aneurysm (AAA) accumulates features of a chronic inflammatory disorder and irreversible destruction of connective tissue. A recent experimental study identified c-Jun N terminal kinase (JNK) as a proximal signaling molecule in the pathogenesis of AAA and vascular dendritic cells as key players in the inflammatory reaction and degradation of the extracellular matrix. Statins can inhibit cell proliferation and vascular inflammation, which might help prevent AAA progression. However, supporting clinical data from human studies are lacking. We hypothesized that atorvastatin might inhibit JNK and dendritic cells, resulting in suppression of inflammatory cells and matrix metalloproteinases (MMPs) in human tissue of AAA.


METHODS
Patients with AAA were randomized to atorvastatin (20mg/day, n=10) and non-treated (n=10) groups. After treatment for 4 weeks, patients underwent abdominal aorta replacement, tissue specimens were obtained, and tissue composition was assessed using immunohistochemistry with quantitative image analysis.


RESULTS
Atorvastatin significantly reduced expression of JNK (1.1% vs. 8.1%, P=0.0002) and dendritic cells (3.2 vs. 7.2, P=0.003) compared to controls. T cells (142 vs. 315, P=0.008), macrophages (13 vs. 24, P=0.048) and immunoreactivity to MMP-2 (7.8% vs. 21%, P=0.049) and MMP-9 (13% vs. 24%, P=0.028) were also suppressed in the atorvastatin group. Serum low-density lipoprotein cholesterol level was decreased by 40% in the atorvastatin group.


CONCLUSIONS
Atorvastatin treatment acutely reduces JNK expression and dendritic cells, resulting in reduced inflammatory cell content and expression of MMPs in the AAA wall.
Kajimoto
Kan
K
Department of Cardiovascular Surgery, Juntendo University, Tokyo, Japan.
Miyauchi
Katsumi
K
Kasai
Takatoshi
T
Shimada
Kazunori
K
Kojima
Yuko
Y
Shimada
Akie
A
Niinami
Hiroshi
H
Amano
Atsushi
A
Daida
Hiroyuki
H
D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D000069059:Atorvastatin; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D011758:Pyrroles / Q000008:administration & dosage*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D006538:Heptanoic Acids; D011758:Pyrroles; D019715:Tissue Inhibitor of Metalloproteinase-1; D000069059:Atorvastatin; D048031:JNK Mitogen-Activated Protein Kinases; D020782:Matrix Metalloproteinases