The elevated expression of osteopontin and NF-κB in human aortic aneurysms and its implication

Abstract

The expression and significance of osteopontin (OPN) and NF-κB in patients with thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) were investigated. Thirteen TAA specimens, 20 AAA specimens and 6 normal aortic specimens were collected. The expression of OPN, nuclear factor-κB P65 (NF-κB P65), urokinase plasminogen activator (uPA), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were detected by using immunohistochemistry and Western blotting was employed to determine the expression of OPN and NF-κB P65. Immunohistochemical results showed that the expression of OPN, NF-κB P65, uPA, MMP-2 and MMP-9 was positive in all TAA and AAA specimens and negative in normal specimens, with the difference being statistically significant (P<0.05). There was no difference in the expression between TAA and AAA specimens (P>0.05). Correlation analysis revealed that there existed a positive correlation between the expression of OPN and that of NF-κB P65, uPA, MMP-2 and MMP-9 and between the expression of NF-κB P65 and that of uPA, MMP-2, MMP-9 (P<0.05). Western blotting demonstrated that OPN and NF-κB P65 were positive in AAA and TAA specimens, and negative in normal specimens with the differences being statistically significant (P<0.05). There were no statistically significant differences in the expression of OPN and NF-κB P65 between AAA and TAA specimens (P>0.05). It was concluded that OPN and NF-κB P65 were involved in the pathogenesis of TAA and AAA. OPN can up-regulate the expression of MMP and uPA via NF-κB signaling pathway thereby accelerating the degradation of extracellular matrix and playing an important role in the pathogenesis and development of TAA and AAA.

Meta-analysis and meta-regression analysis of biomarkers for abdominal aortic aneurysm

“…MMPs degrade extracellular matrix proteins including collagen and elastin, and their expression has been studied widely in relation to AAA. This study found no difference in circulating MMP‐2 levels in patients with AAA compared with controls ( P = 0·590), whereas several studies reported that aortic tissue MMP‐2 was increased in patients with AAA. Circulating MMP‐9 levels were significantly increased in patients with AAA ( P = 0·002), a finding supported by many aortic tissue MMP‐9 studies.…”

“…S1 , supporting information). This is in contrast to aortic tissue MMP‐2 levels, which were significantly increased in six studies, with no difference in only one. Circulating MMP‐2 activity was measured by zymography in two studies, and demonstrated no difference.…”

“…). This finding was supported by five studies that analysed aortic tissue MMP‐9 levels, although two did not find a significant increase. Meta‐regression of circulating MMP‐9 studies demonstrated no correlation with aneurysm diameter ( P = 0·690), consistent with three additional studies; however, one study did report this correlation.…”

“…OPN increases the expression of MMPs, and is involved in collagen synthesis, angiogenesis, neovascularization and calcification. It was significantly increased in both aortic tissue and the circulation of people with AAA.…”

“…In the circulation, both blood 95 and plasma 58 samples demonstrated an increase in OPG levels in patients with AAA, and OPG levels correlated with aneurysm growth rates 92 ; however, no correlation was found with aortic diameter 22 . Levels of osteopontin (OPN) were increased significantly in both aortic tissue 15 and the circulation 9,58,77 . Golledge and colleagues 77 reported an AUC of 0⋅65 for OPN; therefore, despite the findings of this meta-analysis, it may not useful in the clinical setting.…”