Novel technique of aortic banding followed by gene transfer during hypertrophy and heart failure

Monte, Federica del; Butler, Karyn L.; Boecker, Wolfgang; Gwathmey, Judith K.; Hajjar, Roger J.

doi:10.1152/physiolgenomics.00035.2001

Cited by 56 publications

(53 citation statements)

References 15 publications

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“…The study complied with the standards for care and use of animal subjects as stated in the Guide for the Care and Use of Laboratory Animals (National Academy of Sciences, Bethesda, MD). Five days before coronary occlusion, an adenoviral gene was delivered using a catheter-based strategy as described previously (24,25). Briefly, rats were anesthetized, intubated, and mechanically ventilated before surgery.…”

Section: Methodsmentioning

confidence: 99%

Kallikrein/Kinin Protects against Myocardial Apoptosis after Ischemia/Reperfusion via Akt-Glycogen Synthase Kinase-3 and Akt-Bad·14-3-3 Signaling Pathways

Yin

Chao

2005

Journal of Biological Chemistry

109

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Our previous study has shown that human tissue kallikrein protected against ischemia/reperfusion-induced myocardial injury. In the present study, we investigated the protective role of local kallikrein gene delivery in ischemia/reperfusion-induced cardiomyocyte apoptosis and its signaling mechanisms in promoting cardiomyocyte survival. Adenovirus carrying the human tissue kallikrein gene was delivered locally into the heart using a catheter-based technique. Expression and localization of recombinant human kallikrein in rat myocardium after gene transfer were determined immunohistochemically. Kallikrein gene delivery markedly reduced reperfusion-induced cardiomyocyte apoptosis identified by both in situ nick end-labeling and DNA fragmentation. Delivery of the kallikrein gene increased phosphorylation of Src, Akt, glycogen synthase kinase (GSK)-3␤, and Bad(Ser-136) but reduced caspase-3 activation in rat myocardium after reperfusion. The protective effect of kallikrein on apoptosis and its signaling mediators was blocked by icatibant and dominant-negative Akt, indicating a kinin B2 receptor-Akt-mediated event. Similarly, kinin or transduction of kallikrein in cultured cardiomyocytes promoted cell viability and attenuated apoptosis induced by hypoxia/reoxygenation. The effect of kallikrein on cardiomyocyte survival was blocked by dominant-negative Akt and a constitutively active mutant of GSK-3␤, but it was facilitated by constitutively active Akt, catalytically inactive GSK-3␤, lithium, and caspase-3 inhibitor. Moreover, kallikrein promoted Bad⅐14-3-3 complex formation and inhibited Akt-GSK-3␤-dependent activation of caspase-3, whereas caspase-3 administration caused reduction of the Bad⅐14-3-3 complex, indicating an interaction between Akt-GSK-caspase-3 and Akt-Bad⅐14-3-3 signaling pathways. In conclusion, kallikrein/kinin protects against cardiomyocyte apoptosis in vivo and in vitro via Akt-Bad⅐14-3-3 and Akt-GSK-3␤-caspase-3 signaling pathways.

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Section: Methodsmentioning

confidence: 99%

Kallikrein/Kinin Protects against Myocardial Apoptosis after Ischemia/Reperfusion via Akt-Glycogen Synthase Kinase-3 and Akt-Bad·14-3-3 Signaling Pathways

Yin

Chao

2005

Journal of Biological Chemistry

109

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“…We examined resistin expression in rat hearts subject to pressure overload because of thoracic aortic banding (25). Hypertrophy in this model was assessed by determining the ratio of left ventricular weight to body weight (LVW/BW).…”

Section: Resistin Is Increased In Ventricular Tissue From Pressureovementioning

confidence: 99%

Resistin Promotes Cardiac Hypertrophy via the AMP-activated Protein Kinase/Mammalian Target of Rapamycin (AMPK/mTOR) and c-Jun N-terminal Kinase/Insulin Receptor Substrate 1 (JNK/IRS1) Pathways

Kang

Chemaly

Hajjar

et al. 2011

Journal of Biological Chemistry

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Resistin has been suggested to be involved in the development of diabetes and insulin resistance. We recently reported that resistin is expressed in diabetic hearts and promotes cardiac hypertrophy; however, the mechanisms underlying this process are currently unknown. Therefore, we wanted to elucidate the mechanisms associated with resistin-induced cardiac hypertrophy and myocardial insulin resistance. Overexpression of resistin using adenoviral vector in neonatal rat ventricular myocytes was associated with inhibition of AMP-activated protein kinase (AMPK) activity, activation of tuberous sclerosis complex 2/mammalian target of rapamycin (mTOR) pathway, and increased cell size, S6K , a downstream kinase target of mTOR, and increased phosphorylation of the IRS1 serine 636/639 residues, whereas treatment with rapamycin reduced the phosphorylation of these residues. Interestingly, these in vitro signaling pathways were also operative in vivo in ventricular tissues from adult rat hearts overexpressing resistin. These data demonstrate that resistin induces cardiac hypertrophy and myocardial insulin resistance, possibly via the AMPK/mTOR/p70 S6K and apoptosis signal-regulating kinase 1/JNK/IRS1 pathways.

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“…Five days before coronary occlusion, gene delivery was performed with the use of a catheter-based strategy as described. 22,23 Briefly, rats were anesthetized, intubated, and mechanically ventilated before surgery. The chest was entered through a left intercostal approach.…”

Section: Catheter-based Gene Deliverymentioning

confidence: 99%

Adrenomedullin Protects Against Myocardial Apoptosis After Ischemia/Reperfusion Through Activation of Akt-GSK Signaling

2004

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Abstract-Adrenomedullin (AM) is a potent vasoactive peptide and plays an important role in cardiovascular function. In this study, we delivered the AM gene locally into the heart, using a catheter-based technique to investigate the signaling mechanism mediated by AM in protection against cardiomyocyte apoptosis induced by acute ischemia/reperfusion. After adenovirus-mediated gene delivery, highly efficient and specific expression of luciferase, green fluorescent protein, or recombinant human AM was identified in the left ventricle. Delivery of the AM gene 5 days before ischemia/reperfusion attenuated myocardial apoptosis identified by in situ dUTP nick-end labeling and DNA laddering, and the effect was blocked by the AM antagonist human calcitonin gene-related peptide (CGRP 8 to 37). AM gene transfer increased phosphorylation of Akt and glycogen synthase kinase (GSK-3␤) but reduced GSK-3␤ and caspase-3 activities in the heart. The effects of AM on GSK-3␤ and caspase-3 activities were blocked by CGRP (8-37) and by adenovirus containing dominant-negative Akt (DN-Akt). Furthermore, in cultured cardiomyocytes, AM also attenuated apoptosis induced by hypoxia/reoxygenation, which was accompanied by increased phospho-GSK-3␤ but reduced GSK-3 and caspase-3 activities. GSK-3 and caspase-3 activities were both blocked by Ad.DN-Akt and lithium, whereas only caspase-3 was inhibited by its inhibitor Z-VAD. The effects of AM on anti-apoptosis and promoting cell viability were blocked by DN-Akt but not by constitutively active Akt, lithium, or Z-VAD. These results indicate that AM protects against cardiomyocyte apoptosis induced by ischemia/reperfusion injury through the Akt-GSK-caspase signaling pathway.

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Novel technique of aortic banding followed by gene transfer during hypertrophy and heart failure

Cited by 56 publications

References 15 publications

Kallikrein/Kinin Protects against Myocardial Apoptosis after Ischemia/Reperfusion via Akt-Glycogen Synthase Kinase-3 and Akt-Bad·14-3-3 Signaling Pathways

Kallikrein/Kinin Protects against Myocardial Apoptosis after Ischemia/Reperfusion via Akt-Glycogen Synthase Kinase-3 and Akt-Bad·14-3-3 Signaling Pathways

Resistin Promotes Cardiac Hypertrophy via the AMP-activated Protein Kinase/Mammalian Target of Rapamycin (AMPK/mTOR) and c-Jun N-terminal Kinase/Insulin Receptor Substrate 1 (JNK/IRS1) Pathways

Adrenomedullin Protects Against Myocardial Apoptosis After Ischemia/Reperfusion Through Activation of Akt-GSK Signaling

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