The findings suggest that NOX-derived ROS results in increased mito-ROS. Whereas short-term increase in mito-ROS was counteracted by MnSOD, long-term increase in ROS resulted in nitrotyrosine-mediated inactivation of MnSOD, leading to unchecked increase in mito-ROS and loss of Δψm followed by inhibition of endothelial function and proliferation.

Use of MUF was associated with increased inflammatory response, reduced blood loss, and less blood transfusions in adults undergoing coronary artery bypass grafting.

BackgroundThe inflammatory response has been implicated in the pathogenesis of left ventricular (LV) remodeling after myocardial infarction (MI). An anthraquinone compound with anti-inflammatory properties, diacerein inhibits the synthesis and activity of pro-inflammatory cytokines, such as tumor necrosis factor and interleukins 1 and 6. The purpose of this study was to investigate the effects of diacerein on ventricular remodeling in vivo.Methods and ResultsLigation of the left anterior descending artery was used to induce MI in an experimental rat model. Rats were divided into two groups: a control group that received saline solution (n = 16) and a group that received diacerein (80 mg/kg) daily (n = 10). After 4 weeks, the LV volume, cellular signaling, caspase 3 activity, and nuclear factor kappa B (NF-κB) transcription were compared between the two groups. After 4 weeks, end-diastolic and end-systolic LV volumes were reduced in the treatment group compared to the control group (p < .01 and p < .01, respectively). Compared to control rats, diacerein-treated rats exhibited less fibrosis in the LV (14.65%± 7.27% vs. 22.57%± 8.94%; p < .01), lower levels of caspase-3 activity, and lower levels of NF-κB p65 transcription.ConclusionsTreatment with diacerein once a day for 4 weeks after MI improved ventricular remodeling by promoting lower end-systolic and end-diastolic LV volumes. Diacerein also reduced fibrosis in the LV. These effects might be associated with partial blockage of the NF-κB pathway.

PurposeTherapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI.MethodsMale Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed.ResultsEnd-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50.ConclusionTreatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events.