The MMPs are a family of more than 25 species of zinc-dependent proteases that play a pivotal part in collagen degradation

The MMPs are a family of more than 25 species of zinc-dependent proteases that play a pivotal part in collagen degradation. periostin and collagen type III were reduced the MI-S group compared with the MI-group. In addition, TIMP-1 concentration in myocardium was higher in the MI-S group compared with the MI group. Conclusions The predominant result of spironolactone supplementation after MI is related to reductions in collagens, with discrete attenuation of additional remodeling variables. Importantly, this effect may be modulated by periostin and TIMP-1 levels. Introduction Heart failure is a frequent complication of myocardial infarction (MI). Several factors influence the appearance of remaining ventricular dysfunction after MI. However, cardiac remodeling is definitely a major cause of progressive heart failure following coronary occlusion. Importantly, the Bay 11-7821 consequences of cardiac dysfunction after MI are well established, and cardiac dysfunction Bay 11-7821 increases the risk of death by at least 3-collapse. It is well approved that patients who have heart failure and remaining ventricular systolic dysfunction are at higher risk for adverse results, including cardiac rupture, stroke, ventricular arrhythmias, recurrent myocardial infarction, and death, including sudden death [1]. Recent large clinical trials suggest that aldosterone receptor blockade enhances survival and reduces morbidity in individuals with heart failure and reduced ejection portion [2-4]. However, to date, there is a poor understanding of the mechanisms involved in the beneficial effects of aldosterone receptor blockade with this scenario. Therefore, the objective of this study was to analyze the effect of spironolactone on cardiac redesigning after experimental MI; the effect was assessed by matricellular proteins, cardiac collagen amount and distribution, myocardial cells metalloproteinase inhibitor-1 concentration, myocyte hypertrophy, remaining ventricular architecture, hemodynamic recording, and and cardiac function. Materials and Methods All the experiments and procedures were performed in accordance with the National Institute of Healths Guidebook for the Care and Use of Laboratory Animals and were approved by the Animal Ethics Committee of Botucatu Medical School. All efforts were made to minimize suffering. Male, Wistar rats that weighed 200-230 g were assigned to 4 experimental organizations: a control group, in which animals were submitted to simulated surgery (SHAM group; n=9); a group in which animals received spironolactone (20 mg/kg of diet/day time) and were submitted to simulated surgery (SHAM-S group, n=9); a myocardial infarction group, in which animals were submitted to coronary artery ligation (MI group, n=15); and a myocardial infarction group with spironolactone supplementation (MI-S group, n=15). An echocardiographic examination was performed 5 days after myocardial infarction, and there was no morphological or practical difference between the MI organizations (data not demonstrated). Water was supplied concentration The levels of TIMP-1 in the heart homogenates were evaluated by ELISA according to the manufacturers instructions (R & D Systems, Minneapolis, MN, USA). Statistical analysis The data are indicated as the means SD. Comparisons between groups were performed by two-way ANOVA analysis followed by Holm-Sidak. Bay 11-7821 For infarct size assessment, the College students t-test was Bay 11-7821 performed. The data analysis was carried out with SigmaStat for Windows v2.03 Rabbit Polyclonal to PPP4R1L (SPSS Inc., Chicago, IL). The significance level was arranged at P 0.05. Results There was no difference in infarct size between the MI and MI-S organizations (MI: 33.17 13.39% MI-S: 25.06 13.64%; p=0.174). The echocardiographic data are outlined in Table 1. The animals in the MI group experienced higher ideals for remaining cardiac chambers corrected by body weight, higher LVMI and lower relative wall thicknesses compared with the SHAM group. In addition, diastolic and systolic functions were worse in.