Western blot and qRT-PCR analyses demonstrated that ADAMTS16 was significantly up-regulated in mice with transverse aortic constriction (TAC) associated with left ventricular hypertrophy and heart failure, which was correlated with increased expression of Mmp2, Mmp9, Col1a1 and Col3a1.
Subsequent gene/ncRNA expression analysis was assessed using quantitative reverse transcription polymerase chain reaction and revealed 6 genes: 4 hypermethylated ( HEY2, MSR1, MYOM3, and COX17), 2 hypomethylated ( CTGF and MMP2); and 2 microRNA: 1 hypermethylated (miR-24-1), 1 hypomethylated (miR-155) with significantly upregulated or downregulated expression levels consistent with the direction of methylation in the particular HF subgroup.
Specific matrix metalloproteinases (MMP-2, MMP-9) and inflammatory biomarkers (hsCRP, IL-6) were found to be consistently up-regulated in severe mitral valve regurgitation (MR) and are associated with mortality in heart failure patients.
At the same time MMP-2 and MMP-9 circulating levels can serve as indicators of efficiency of the therapy provided to HF patients, as well as for identification of patients who could profit from particular therapeutic intervention via modification of MMP pathway.