RESUMO
This study evaluated the role of the mesenchymal stem cells derived from adipose tissue (MSCs) in provoked ventricular arrhythmias (VAs) in animals with myocardial infarction (MI). The experimental groups were: sham, subjected to sham surgery and intramyocardial saline injection; MIV, infarcted rats subjected to intramyocardial saline injection; MI + MSCs, infarcted rats subjected to intramyocardial MSCs injection. Injections were performed two days after infarction and the arrhythmogenic inducibility experiment was performed the next day. Only 35% of the MI + MSCs group developed VAs, while the one in the MIV group was 65%. The proportion of nonsustained ventricular tachycardia, sustained tachycardia, and ventricular fibrillation was similar between the infarcted groups, but MSCs animals had shorter duration of nonsustained ventricular tachycardia. However, MSCs increased connexin 43 content in the remote area, even above the levels found in the sham group. MSCs prevented the increase of IL-1ß in the different areas of the myocardium. There was higher carbonylation and content of 4-hydroxynonenal (4-HNE, a marker of lipoperoxidation) in the myocardium of infarcted rats, but MSCs attenuated the increase of 4-HNE in the infarcted area. In conclusion, MSCs have a protective effect against the development of arrhythmias, but do not imply a significant benefit for animals that have developed VAs. It is possible to think that the cardioprotection of MSCs involves anti-inflammatory/oxidative actions and improvement in the formation of communicating junctions.Graphical abstract.
RESUMO
Stem cell (SC) therapy is a promising approach to improve post-myocardial infarction (MI) cardiac remodeling, but the proinflammatory microenvironment may lead to SC loss and, therefore, may have a negative impact on therapy. It appears that exercise training (ET) improves myocardial microenvironment for SC transplantation. Therefore, we tested the effect of ET on post-infarction retention of adipose-derived SCs (ADSCs) and its combined effects on the inflammatory microenvironment. Fischer-344 female rats were randomized to one of the following groups: Sham; sedentary coronary occlusion who did not receive ADSCs (sMI); sedentary coronary occlusion who received ADSCs; exercise coronary occlusion who received ADSCs. Rats were trained nine weeks prior to MI, followed by ADSCs transplantation. The MI led to left ventricle (LV) dilation and dysfunction, myocardial hypertrophy and fibrosis, and increased proinflammatory profile compared to Sham rats. Conversely, ADSCs transplanted rats exhibited, better morphological and functional LV parameters; inhibition of myocardial hypertrophy and fibrosis; and attenuation of proinflammatory cytokines (interleukins 1ß and 10, tumor necrosis factor α, and transforming growth factor ß) in the myocardium compared to sMI rats. Interestingly, ET enhanced the effect of ADSCs on interleukin 10 expression. There was a correlation between cytokine expression and myocardial ADSCs retention. The. ET enhanced the beneficial effects of ADSCs in infarcted myocardium, which was associated with higher ADSCs retention. These findings highlight the importance of ET in myocardial retention of ADSCs and attenuation of cardiac remodeling post-infarction. Cytokine analysis suggests improvement in ET-linked myocardial microenvironment based on its anti-inflammatory action.