The overexpression of α1-antitrypsin or the exogenous α1-antitrypsin treatment exhibits an anti-oxidative stress role, evaluated by increased eNOS expression and by decreased MMP9 expression, implicated in HF.
Metalloproteinases and their inhibitors, such as MMP9 and TIMP-1, assist in maintaining the extracellular matrix, leading to tissue remodeling observed after HF.
The contractile responses induced by CCh, ATP and EFS were greater in detrusor muscle (DSM) from HF rats. mRNA expression for muscarinic receptors (M2 and M3) was higher in DSM only after 12 weeks of ACF, in addition to MMP9 and TGF-beta.
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.
Cardiac function in class III and above, increased NT-proBNP, increased MMP-9 and decreased LVEF were relevant risk factors and independent risk factors for heart failure in patients with different cardiac functions.
A multivariate Cox proportional hazard model showed that high MMP-9 values were an independent predictor of HF events (hazard ratio, 3.73; 95% confidence interval (CI), 1.03-13.46; P = 0.043).
Patients were in New York Heart Association (NYHA) functional class III or IV heart failure showed a significantly higher MMP9 levels (1,348.0±337.2 <i>vs</i>.
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.
Given that MMP-9 is an AP-1 target gene involved in cardiac remodeling, myocardial dysfunction and progression of heart failure, these findings suggest that miR-146a might be a new and promising therapeutic tool for treating cardiac disorders associated with enhanced inflammation in the heart.
Therefore, mixed adrenoceptor blockade may reduce remodeling in heart failure as a direct consequence of a beta-adrenoceptor-mediated reduction in MMP-9 transcription.