Ischemic post-conditioning reduces infarct size of the in vivo rat heart: role of PI3-K, mTOR, GSK-3β, and apoptosis

2010 ◽  
Vol 339 (1-2) ◽  
pp. 135-147 ◽  
Author(s):  
Claudia Wagner ◽  
Diana Tillack ◽  
Gregor Simonis ◽  
Ruth H. Strasser ◽  
Christof Weinbrenner
Keyword(s):  
Infarct Size ◽  
Rat Heart ◽  
Gsk 3Β ◽  
In Vivo Rat Heart

Cyclosporine A at reperfusion fails to reduce infarct size in the in vivo rat heart

2013 ◽  
Vol 108 (5) ◽  
Author(s):  
Damien Paulis ◽  
Pascal Chiari ◽  
Geoffrey Teixeira ◽  
Elisabeth Couture-Lepetit ◽  
Maryline Abrial ◽  
...  
Keyword(s):  
Infarct Size ◽  
Cyclosporine A ◽  
Rat Heart ◽  
Reduce Infarct Size ◽  
In Vivo Rat Heart

Myocardial reperfusion injury management: erythropoietin compared with postconditioning

2009 ◽  
Vol 297 (6) ◽  
pp. H2035-H2043 ◽  
Author(s):  
Sophie Tamareille ◽  
Nehmat Ghaboura ◽  
Frederic Treguer ◽  
Dalia Khachman ◽  
Anne Croué ◽  
...  
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Myocardial Reperfusion ◽  
Myocardial Reperfusion Injury ◽  
Gsk 3Β ◽  
Developed Pressure

Ischemic postconditioning (IPost) and erythropoietin (EPO) have been shown to attenuate myocardial reperfusion injury using similar signaling pathways. The aim of this study was to examine whether EPO is as effective as IPost in decreasing postischemic myocardial injury in both Langendorff-isolated-heart and in vivo ischemia-reperfusion rat models. Rat hearts were subjected to 25 min ischemia, followed by 30 min or 2 h of reperfusion in the isolated-heart study. Rats underwent 45 min ischemia, followed by 24 h of reperfusion in the in vivo study. In both studies, the control group ( n = 12; ischemia-reperfusion only) was compared with IPost ( n = 16; 3 cycles of 10 s reperfusion/10 s ischemia) and EPO ( n = 12; 1,000 IU/kg) at the onset of reperfusion. The following resulted. First, in the isolated hearts, IPost or EPO significantly improved postischemic recovery of left ventricular developed pressure. EPO induced better left ventricular developed pressure than IPost at 30 min of reperfusion (73.18 ± 10.23 vs. 48.11 ± 7.92 mmHg, P < 0.05). After 2 h of reperfusion, the infarct size was significantly lower in EPO-treated hearts compared with IPost and control hearts (14.36 ± 0.60%, 19.11 ± 0.84%, and 36.21 ± 4.20% of the left ventricle, respectively; P < 0.05). GSK-3β phosphorylation, at 30 min of reperfusion, was significantly higher with EPO compared with IPost hearts. Phosphatidylinositol 3-kinase and ERK1/2 inhibitors abolished both EPO- and IPost-mediated cardioprotection. Second, in vivo, IPost and EPO induced an infarct size reduction compared with control (40.5 ± 3.6% and 28.9 ± 3.1%, respectively, vs. 53.7 ± 4.3% of the area at risk; P < 0.05). Again, EPO decreased significantly more infarct size and transmurality than IPost ( P < 0.05). In conclusion, with the use of our protocols, EPO showed better protective effects than IPost against reperfusion injury through higher phosphorylation of GSK-3β.

KATP channels in rat heart: blockade of ischemic and acetylcholine-mediated preconditioning by glibenclamide

1996 ◽  
Vol 271 (1) ◽  
pp. H23-H28 ◽  
Author(s):  
Y. Z. Qian ◽  
J. E. Levasseur ◽  
K. Yoshida ◽  
R. C. Kukreja
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Rat Heart ◽  
Katp Channel ◽  
Katp Channels ◽  
Ischemia And Reperfusion ◽  
Area At Risk ◽  
Specific Antagonist ◽  
Percent Area

The objective of this study was to examine if the opening of ATP-sensitive K+ (KATP) channels play an important role in ischemic preconditioning (PC) in the rat heart. A second goal was to test the role of acetylcholine (ACh) in mimicking PC and test if it could be blocked by KATP antagonist. Glibenclamide, a specific antagonist of the KATP channel, was given as two doses of 0.3 mg/kg each at 60 and 30 min before PC. Six groups of rats were subjected to ischemia and reperfusion (I/R) using these protocols: 1) control (I/R), 30-min ischemia followed by 90-min reperfusion (n = 6 rats); 2) preconditioned hearts given 5-min ischemia 10 min before I/R (n = 9 rats); 3) glibenclamide (0.3 mg/kg) treatment 60 and 30 min before PC (n = 13 rats); 4) glibenclamide treatment before I/R (n = 15 rats); 5) ACh infusion for 5 min (18 micrograms/ml) at a rate of 0.15 ml/min followed by equilibration for 10 min before I/R, n = 13 rats; and 6) glibenclamide treatment before ACh infusion followed by I/R (n = 11 rats). Preconditioning reduced the infarcted area (expressed as percent area at risk) from 42.0 +/- 4.4% in control to 8.7 +/- 6% (mean +/- SE, P < 0.05). Glibenclamide blocked the protection conferred by PC (39.1 +/- 4.5%, P < 0.05) without having a significant effect on control nonpreconditioned hearts. ACh infusion in lieu of PC also reduced infarct size to 25.0 +/- 5.63% (P < 0.05 compared with control), which was again blocked by glibenclamide (44.2 +/- 5.0%, P < 0.05). The data suggest that opening of KATP channels for ischemic and ACh-mediated preconditioning is also important in the rat heart.

Angiotensin-(1–7) stimulates the phosphorylation of JAK2, IRS-1 and Akt in rat heart in vivo: role of the AT1 and Mas receptors

2007 ◽  
Vol 293 (2) ◽  
pp. H1154-H1163 ◽  
Author(s):  
Jorge F. Giani ◽  
Mariela M. Gironacci ◽  
Marina C. Muñoz ◽  
Clara Peña ◽  
Daniel Turyn ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Rat Heart ◽  
Inhibitory Effect ◽  
Janus Kinase ◽  
Ang Ii ◽  
Signaling Crosstalk ◽  
Akt Phosphorylation ◽  
Jak2 Inhibitor

Angiotensin (ANG) II exerts a negative modulation on insulin signal transduction that might be involved in the pathogenesis of hypertension and insulin resistance. ANG-(1–7), an endogenous heptapeptide hormone formed by cleavage of ANG I and ANG II, counteracts many actions of ANG II. In the current study, we have explored the role of ANG-(1–7) in the signaling crosstalk that exists between ANG II and insulin. We demonstrated that ANG-(1–7) stimulates the phosphorylation of Janus kinase 2 (JAK2) and insulin receptor substrate (IRS)-1 in rat heart in vivo. This stimulating effect was blocked by administration of the selective ANG type 1 (AT1) receptor blocker losartan. In contrast to ANG II, ANG-(1–7) stimulated cardiac Akt phosphorylation, and this stimulation was blunted in presence of the receptor Mas antagonist A-779 or the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin. The specific JAK2 inhibitor AG-490 blocked ANG-(1–7)-induced JAK2 and IRS-1 phosphorylation but had no effect on ANG-(1–7)-induced phosphorylation of Akt, indicating that activation of cardiac Akt by ANG-(1–7) appears not to involve the recruitment of JAK2 but proceeds through the receptor Mas and involves PI3K. Acute in vivo insulin-induced cardiac Akt phosphorylation was inhibited by ANG II. Interestingly, coadministration of insulin with an equimolar mixture of ANG II and ANG-(1–7) reverted this inhibitory effect. On the basis of our present results, we postulate that ANG-(1–7) could be a positive physiological contributor to the actions of insulin in heart and that the balance between ANG II and ANG-(1–7) could be relevant for the association among insulin resistance, hypertension, and cardiovascular disease.

Noradrenaline Protects In Vivo Rat Heart Against Infarction and Ventricular Arrhythmias Via Nitric Oxide and Reactive Oxygen Species

2011 ◽  
Vol 169 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Alireza Imani ◽  
Mahdieh Faghihi ◽  
Sayyed Shahabeddin Sadr ◽  
Somayeh Sadeghi Niaraki ◽  
Ali Mohammad Alizadeh
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Rat Heart ◽  
Ventricular Arrhythmias ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
In Vivo Rat Heart

scholarly journals Evidence for a Functional Role of Angiotensin II Type 2 Receptor in the Cardiac Hypertrophic Process In Vivo in the Rat Heart

Circulation ◽  
2003 ◽  
Vol 108 (19) ◽  
pp. 2414-2422 ◽  
Author(s):  
Zoltán Lakó-Futó ◽  
István Szokodi ◽  
Balázs Sármán ◽  
Gábor Földes ◽  
Heikki Tokola ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Rat Heart ◽  
Functional Role

scholarly journals Glycogen synthase kinase-3β/β-catenin signaling regulates neonatal lung mesenchymal stromal cell myofibroblastic differentiation

2012 ◽  
Vol 303 (5) ◽  
pp. L439-L448 ◽  
Author(s):  
Antonia P. Popova ◽  
J. Kelley Bentley ◽  
Anuli C. Anyanwu ◽  
Michelle N. Richardson ◽  
Marisa J. Linn ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Glycogen Synthase ◽  
Smooth Muscle Actin ◽  
Muscle Actin ◽  
Neonatal Lung ◽  
Gsk 3Β ◽  
Tgf Β1 ◽  
Myofibroblastic Differentiation

In bronchopulmonary dysplasia (BPD), alveolar septa are thickened with collagen and α-smooth muscle actin-, transforming growth factor (TGF)-β-positive myofibroblasts. We examined the biochemical mechanisms underlying myofibroblastic differentiation, focusing on the role of glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway. In the cytoplasm, β-catenin is phosphorylated on the NH2 terminus by constitutively active GSK-3β, favoring its degradation. Upon TGF-β stimulation, GSK-3β is phosphorylated and inactivated, allowing β-catenin to translocate to the nucleus, where it activates transcription of genes involved in myofibroblastic differentiation. We examined the role of β-catenin in TGF-β1-induced myofibroblastic differentiation of neonatal lung mesenchymal stromal cells (MSCs) isolated from tracheal aspirates of premature infants with respiratory distress. TGF-β1 increased β-catenin expression and nuclear translocation. Transduction of cells with GSK-3β S9A, a nonphosphorylatable, constitutively active mutant that favors β-catenin degradation, blocked TGF-β1-induced myofibroblastic differentiation. Furthermore, transduction of MSCs with ΔN-catenin, a truncation mutant that cannot be phosphorylated on the NH2 terminus by GSK-3β and is not degraded, was sufficient for myofibroblastic differentiation. In vivo, hyperoxic exposure of neonatal mice increases expression of β-catenin in α-smooth muscle actin-positive myofibroblasts. Similar changes were found in lungs of infants with BPD. Finally, low-passage unstimulated MSCs from infants developing BPD showed higher phospho-GSK-3β, β-catenin, and α-actin content compared with MSCs from infants not developing this disease, and phospho-GSK-3β and β-catenin each correlated with α-actin content. We conclude that phospho-GSK-3β/β-catenin signaling regulates α-smooth muscle actin expression, a marker of myofibroblast differentiation, in vitro and in vivo. This pathway appears to be activated in lung mesenchymal cells from patients with BPD.

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