MiR-30c-1-3p Targets Matrix Metalloproteinase 9 Involved into the Rupture of Abdominal Aortic Aneurysms

Author(s):  
Lin Yang ◽  
Hong-gang Sui ◽  
Meng-meng Wang ◽  
Jia-yin Li ◽  
Xiao-feng He ◽  
...  

Abstract Abdominal aortic aneurysm (AAA) can be fatal if ruptured, but there is no predictive biomarker. Our aim was to evaluate the prognostic potential of microRNAs (miRNAs/miRs) in an AAA mouse model and patients with unruptured AAA (URAAA) and ruptured AAA (RAAA). Among the 64 miRNAs differentially expressed in mice with AAA compared to control, miR-30c-1-3p, miR-432-3p, miR-3154, and miR-379-5p had high homology with human miRNAs. MiR-30c-1-3p plasma levels were significantly lower in patients with RAAA than in those with URAAA or control and tended to negatively correlate with the maximum aortic diameter (r = -0.3153, P = 0.06109). Mir-30c-1-3p targeted matrix metalloproteinase (MMP)-9 mRNA through the coding region and downregulated its expression in vitro. MMP-9 plasma concentrations were significantly higher in the RAAA group than in the URAAA group (P < 0.001) and were negatively associated with miR-30c-1-3p levels (r = -0.3671, P = 0.01981) and positively – with the maximal aortic diameter (r = 0.6251, P < 0.0001). The optimal cutoff values for MMP-9 expression and the maximal aortic diameter were 461.08 ng/ml and 55.95 mm, with areas under the curve of 0.816 and 0.844, respectively. Our results indicate that plasma levels of mir-30c-1-3p and MMP-9 may be candidate biomarkers of AAA progression.

2008 ◽  
Vol 86 (7) ◽  
pp. 431-437 ◽  
Author(s):  
Petra J. Mateos-Cáceres ◽  
Antonio J. López-Farré ◽  
Pilar C. Morata ◽  
Priscila Ramos-Mozo ◽  
Carlos Macaya ◽  
...  

The effect of pravastatin on matrix metalloproteinase-9 (MMP-9) and the level of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 was studied in explants of human abdominal aortic aneurysm (AAA) obtained from 13 patients. The effect of pravastatin on the apoptotic status of human AAA explants was also examined. Total MMP-9 content did not differ in human AAA explants incubated in vitro in the presence or absence of pravastatin (10−6mol/L) for 48 h. TIMP-1 levels were significantly increased in pravastatin-incubated AAA explants, but TIMP-2 production was not modified by pravastatin. Western blot experiments showed that, whereas Bax expression was increased in pravastatin-incubated AAA explants, the expression of Bcl-2 was not modified. On the other hand, the ratio of the expression of Bax to Bcl-2, an apoptotic index, was not modified by pravastatin. In the human AAA explants, the increase in Bax expression, but not the increase in TIMP-1 expression elicited by pravastatin, was reversed by l-mevalonate, a downstream HMG-CoA reductase metabolite, suggesting that the expression of Bax and TIMP-1 followed HMG-CoA reductase-dependent and -independent pathways, respectively. In conclusion, pravastatin increases both TIMP-1 and Bax expression in human AAA explants without changes in either MMP-9 activity or the apoptotic status.


2017 ◽  
Vol 81 (6) ◽  
pp. 888-890 ◽  
Author(s):  
Deborah A. Howatt ◽  
Maya Dajee ◽  
Xiaojie Xie ◽  
Jessica Moorleghen ◽  
Debra L. Rateri ◽  
...  

Vascular ◽  
2004 ◽  
Vol 12 (05) ◽  
pp. 312 ◽  
Author(s):  
Maurizio Taurino ◽  
Vincenzo Visco ◽  
Salvatore Raffa ◽  
Benedetto Ricci ◽  
Massimo Ruggiero ◽  
...  

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