Type 2 iodothyronine deiodinase is upregulated in rat slow- and fast-twitch skeletal muscle during cold exposure.

During cold acclimation, shivering is progressively replaced by nonshivering thermogenesis. Brown adipose tissue (BAT) and skeletal muscle are relevant for nonshivering thermogenesis, which depends largely on thyroid hormone. Since the skeletal muscle fibers progressively adapt to cold exposure through poorly defined mechanisms, our intent was to determine whether skeletal muscle type 2 deiodinase (D2) induction could be implicated in the long-term skeletal muscle cold acclimation. We demonstrate that in the red oxidative soleus muscle, D2 activity increased 2.3-fold after 3 days at 4°C together with the brown adipose tissue D2 activity, which increased 10-fold. Soleus muscle and BAT D2 activities returned to the control levels after 10 days of cold exposure, when an increase of 2.8-fold in D2 activity was detected in white glycolytic gastrocnemius but not in red oxidative gastrocnemius fibers. Propranolol did not prevent muscle D2 induction, but it impaired the decrease of D2 in BAT and soleus after 10 days at 4°C. Cold exposure is accompanied by increased oxygen consumption, UCP3, and PGC-1α genes expression in skeletal muscles, which were partialy prevented by propranolol in soleus and gastrocnemius. Serum total and free T3 is increased during cold exposure in rats, even after 10 days, when BAT D2 is already normalized, suggesting that skeletal muscle D2 activity contributes significantly to circulating T3 under this adaptive condition. In conclusion, cold exposure is accompanied by concerted changes in the metabolism of BAT and oxidative and glycolytic skeletal muscles that are paralleled by type 2 deiodinase activation.

Adipose-derived stromal cell therapy improves cardiac function after coronary occlusion in rats.

Recent studies have identified adipose tissue as a new source of mesenchymal stem cells for therapy. The purpose of this study was to investigate the therapy with adipose-derived stromal cells (ASCs) in a rat model of healed myocardial infarction (MI). ASCs from inguinal subcutaneous adipose tissue of male Wistar rats were isolated by enzymatic digestion and filtration. Cells were then cultured until passage 3. Four weeks after ligation of the left coronary artery of female rats, a suspension of either 100 µl with phosphate-buffered saline (PBS) + Matrigel + 2 × 10(6) ASCs labeled with Hoechst (n = 11) or 100 µl of PBS + Matrigel (n = 10) was injected along the borders of the ventricular wall scar tissue. A sham-operated group (n = 5) was submitted to the same surgical procedure except permanent ligation of left coronary artery. Cardiac performance was assessed by electro- and echocardiogram. Echo was performed prior to injections (baseline, BL) and 6 weeks after injections (follow-up, FU), and values after treatment were normalized by values obtained before treatment. Hemodynamic measurements were performed 6 weeks after injections. All infarcted animals exhibited cardiac function impairment. Ejection fraction (EF), shortening fractional area (SFA), and left ventricular akinesia (LVA) were similar between infarcted groups before treatment. Six weeks after therapy, ASC group showed significant improvement in all three ECHO indices in comparison to vehicle group. In anesthetized animals dp/dt(+) was also significantly higher in ASCs when compared to vehicle. In agreement with functional improvement, scar area was diminished in the ASC group. We conclude that ASCs improve cardiac function in infarcted rats when administered directly to the myocardium.

G-CSF does not improve systolic function in a rat model of acute myocardial infarction.

OBJECTIVE: Granulocyte colony-stimulating factor (G-CSF) has been reported to improve cardiac performance by increasing the number of bone marrow stem cell in the peripheral circulation. The aim of this study was to investigate the impact of G-CSF administration on cardiac function in a rat model of acute myocardial infarction. METHODS: Recombinant human G-CSF (Filgrastim, 100 microg/kg, sc) twice a day during seven consecutive days (G-CSF group, n=13) or vehicle (control group, n=10) was administrated three hours after left anterior coronary artery ligation. Cardiac performance was evaluated 19-21 days after myocardial infarction by electro- and echocardiography, hemodynamic and treadmill exercise test. RESULTS: Both infarcted groups exhibit impaired cardiac function compared to sham-operated rats. Moreover, all cardiac functional parameters were not statistically different between G-CSF and infarcted group at resting conditions as well as after treadmill exercise stress test. There was no sign of cardiac regeneration and infarct size was not different on histological analysis between groups. CONCLUSIONS: These data clearly shows that G-CSF treatment was unable to prevent cardiac remodeling or to improve cardiovascular function in a rat model of acute myocardial infarction, by permanent LAD ligation, despite bone marrow stem cell mobilization.