BackgroundCardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs) with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI).Methodology/Principal Findings 99mTc-labeled ASCs (1×106 cells) isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C), or culture medium (ASC/M) as vehicle, and cell body distribution was assessed 24 hours later by γ-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8±2.0 and 26.8±2.4% vs. 4.8±0.7%, respectively). Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV) perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT) and control groups (culture medium, fibrin, or collagen alone). Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV) and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW), a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress.ConclusionsWe provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administrating co-injection of ASCs with biopolymers.

Background: Myocardial infarction (MI) is accompanied by cardiac growth, increased collagen deposition, cell death and new vascularization of the cardiac tissue, which results in reduced ventricular compliance. The MiRNA-29 family (29a, 29b, and 29c) targets mRNAs that encode collagens and other proteins involved in fibrosis. In this study we assessed the effects of swimming training (ST) on expression of the cardiac miRNA-29 family and on genes encoding collagen after MI in rats. Methods: ST consisted of 60 min/day/10 weeks and began four weeks after MI. MiRNA and collagen expression analysis were performed in the infarcted region (IR), border region (BR) of the infarcted region and in the remote myocardium (RM) of the left ventricle. Results: MiRNA-29a expression increased 32% in BR and 52% in RM in the TR-INF compared with SED-INF. MiRNA-29c increased by 63% in BR and 55% in RM in TR-INF compared with SED-INF group. COL IAI and COL IIIAI decreased by 63% and 62% in TR-INF, respectively, compared with SED-INF. COLIIIAI expression decreased by 16% in TR-INF compared with SED-INF. Conclusion: Altogether, our results showed that ST restores cardiac miRNA-29 (a and c) levels and prevents COL IAI and COL IIIAI expression in BR and RM, which may contribute to the improvement in ventricular function induced by swimming training, after MI.

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Myocardial hypertrophy and dysfunction occur in response to excessive catecholaminergic drive. Adverse cardiac remodelling is associated with activation of proinflammatory cytokines in the myocardium. To test the hypothesis that exercise training can prevent myocardial dysfunction and production of proinflammatory cytokines induced by β-adrenergic hyperactivity, male Wistar rats were assigned to one of the following four groups: sedentary non-treated (Con); sedentary isoprenaline treated (Iso); exercised non-treated (Ex); and exercised plus isoprenaline (Iso+Ex). Echocardiography, haemodynamic measurements and isolated papillary muscle were used for functional evaluations. Real-time RT-PCR and Western blot were used to quantify tumour necrosis factor α, interleukin-6, interleukin-10 and transforming growth factor β 1 (TGF-β 1 ) in the tissue. NF-κB expression in the nucleus was evaluated by immunohistochemical staining. The Iso rats showed a concentric hypertrophy of the left ventricle (LV). These animals exhibited marked increases in LV end-diastolic pressure and impaired myocardial performance in vitro, with a reduction in the developed tension and maximal rate of tension increase and decrease, as well as worsened recruitment of the Frank-Starling mechanism. Both gene and protein levels of tumour necrosis factor α and interleukin-6, as well as TGF-β 1 mRNA, were increased. In addition, the NF-κB expression in the Iso group was significantly raised. In the Iso+Ex group, the exercise training had the following effects: (1) it prevented LV hypertrophy; (ii) it improved myocardial contractility; (3) it avoided the increase of proinflammatory cytokines and improved interleukin-10 levels; and (4) it attenuated the increase of TGF-β 1 mRNA. Thus, exercise training in a model of β-adrenergic hyperactivity can avoid the adverse remodelling of the LV and inhibit inflammatory cytokines. Moreover, the cardioprotection is related to beneficial effects on myocardial performance. Abbreviations CSA, cross-sectional area; +dP/dt, maximal positive time derivate of the developed pressure; −dP/dt, maximal negative time derivate of the developed pressure; DT, developed tension; +dT/dt, maximal rate of tension increase; −dT/dt, maximal rate of tension decrease; FS, left vetricular fractional shortening; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HR, heart rate; IL-6, interleukin-6; IL-10, interleukin-10; L max , maximal length; LV, left ventricle; LVEDD, left vetricular end-diastolic diameter; LVEDP, left vetricular end-diastolic pressure; LVESD, left vetricular end-systolic diameter; LVPWd, diastolic left vetricular posterior wall thickness; LVPWs, systolic left vetricular posterior wall thickness; LVSP, left vetricular systolic pressure; MAP, mean arterial pressure; NF-κB, nuclear factor-κB; RT, resting tension; TGF-β 1 , transforming growth factor β 1 ; TNF-α, tumour necrosis factor α.

1. The aim of the present study was to evaluate the effect of swimming on myocardial remodelling after myocardial infarction (MI) in female rats induced by coronary occlusion, which was not performed in sham rats. 2. Rats were divided in six groups, three sedentary (sham (SSh; n = 14), moderate infarct (SMI; n = 8) and large infarct (SLI; n = 10)) and three trained (sham (TSh; n = 16), moderate infarct (TMI; n = 9) and large infarct (TLI; n = 8)) groups. Training (8 weeks, 60 min/day, 5 days/week) was initiated 4 weeks after MI or sham operation. Training did not affect mortality rate, but attenuated the increases in atrial/bodyweight (SSh: 0.07 +/- 0.02; TSh: 0.07 +/- 0.02; SMI: 0.11 +/- 0.03; TMI: 0.09 +/- 0.03; SLI: 0.17 +/- 0.09; TLI: 0.10 +/- 0.05 mg/g) and right ventricular/bodyweight (SSh: 0.15 +/- 0.02; TSh: 0.17 +/- 0.02; SMI: 0.17 +/- 0.07; TMI: 0.20 +/- 0.03; SLI: 0.29 +/- 0.13; TLI: 0.22 +/- 0.08 mg/g) ratios. Myocardial infarction increased pulmonary and myocardial water content in infarcted sedentary animals, whereas no changes were observed in trained infarcted rats. Sedentary infarcted rats showed inotropic and lusitropic depression proportional to the size of the infarct (SSh > SMI > SLI), whereas no differences were noted in trained rats (TLI = TMI = TSh). Indeed, in sedentary rats there was depression of +dT/dt (SSh: 68 +/- 25; TSh: 72 +/- 21; SMI: 53 +/- 20; TMI: 77 +/- 30; SLI: 33 +/- 15; TLI: 57 +/- 22 g/mm(2) per s) and -dT/dt (SSh: 33 +/- 13; TSh: 36 +/- 11; SMI: 24 +/- 5; TMI: 35 +/- 11; SLI: 15 +/- 4; TLI: 32 +/- 11 g/mm(2) per s) compared with trained rats. 3. In conclusion, swimming clearly favoured post-MI cardiac remodelling, attenuated myocardial hypertrophy, contractile and relaxation dysfunction and prevented pulmonary congestion.

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