Intrapericardial IGF-I Improves Cardiac Function in an Ovine Model of Chronic Heart Failure

Matthews, Kenneth G.; Devlin, Gerard; Stuart, Selwyn; Jensen, Joergen L.; Doughty, Robert N.; Conaglen, John V.; Bass, J. J.

doi:10.1016/j.hlc.2005.02.002

Cited by 17 publications

(13 citation statements)

References 29 publications

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“…30 In addition, IGF-1 exerts cardioprotective effects and improves cardiac function in different animal models with cardiac infarction and heart failure. [49][50][51][52][53][54][55] Since in this setting the Ub-pathway has been implicated, [56][57][58][59] one could hypothesize that the cardioprotective effects of IGF-1 detected in those conditions are mediated not only through increased cell survival and protein synthesis but also through regulation of the Ub-pathway.…”

Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor-1 restores dexamethasone-induced heart growth arrest in rats: the role of the ubiquitin pathway

Chrysis¹,

Chagin²,

Sävendahl³

2011

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ObjEctIvE: In skeletal muscle, glucocorticoids induce catabolism and proteolysis which is accomplished via the ubiquitin (Ub) proteolytic pathway. cardiac muscle is a striated muscle which, compared to skeletal muscle, more abundantly expresses components of the Ub pathway, thus suggesting an important role for this pathway in heart physiology. the aim of our study was to explore the role of the Ub pathway in heart muscle physiology. DEsIGN: We treated rats for three days with a pharmacologic dose of dexamethasone (DEXA) 0.5mg/100g body weight (bW). An attempt was also made to counteract the DEXA effect by co-treatment with insulinlike growth factor-1 (IGF-1; 0.35mg/100g bW). rEsULts: DEXA treatment caused a 7.8% decrease in heart weight compared to control (p<0.05) and also increased heart tissue levels of the ubiquitin-conjugating enzyme E2 and the 20s proteasome protein. Myofibrillar proteins degraded by the ubiquitin pathway (α-actin, myoglobin, and troponin 1) were all decreased by DEXA, while ubiquitinated forms of α-actin were increased. Co-treatment with IGF-1 completely prevented DEXA-induced decrease in heart weight, an effect which was accompanied by decreased heart tissue levels of several ubiquitinated proteins including α-actin, the 20S proteasome protein, E2-14kDa mrNA, and c-3 proteasome subunit mrNA, while the levels of non-ubiquinated α-actin, myoglobin, and troponin 1 were all partially restored. CONCLUSION: these results demonstrate that DEXA activates the ubiquitin proteolytic pathway in the heart and that IGF-1 efficiently counteracts this effect. Our findings reveal a possible mechanism for the anti-proteolytic actions of IGF-1 and its cardioprotective role involving the Ub pathway.

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Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor-1 restores dexamethasone-induced heart growth arrest in rats: the role of the ubiquitin pathway

Chrysis¹,

Chagin²,

Sävendahl³

2011

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“…Based on these observations, post-myocardial infarction cardiac repair strategies have been implemented, inducing activation of the GH/IGF-1 axis [21]. Although treatments using either GH [3,4,[6][7][8][9][10] or IGF-1 [22,23] in the post-myocardial infarction setting have been reported, no study has previously directly compared the effects of the two approaches on left ventricular remodelling indices.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, most studies previously evaluating GH/IGF-1 axis activation post-myocardial infarction, concentrated on the effects of GH [3,4,[6][7][8][9][10]; these studies reported an improved left ventricular function and prognosis after GH treatment [3,4,[6][7][8][9][10]. In contrast, data from studies of IGF-1 administration post-myocardial infarction are limited [22,23]. In an ovine model of chronic myocardial infarction, intrapericardial (but not subcutaneous) delivery of IGF-1 improved left ventricular function, with sustained results after cessation of treatment [23].…”

Section: Main Findings and Comparison With Previous Studiesmentioning

confidence: 99%

“…In contrast, data from studies of IGF-1 administration post-myocardial infarction are limited [22,23]. In an ovine model of chronic myocardial infarction, intrapericardial (but not subcutaneous) delivery of IGF-1 improved left ventricular function, with sustained results after cessation of treatment [23]. In rats, intraperitoneal infusion of IGF-1 failed to improve ejection fraction, despite an increase in stroke volume [22].…”

Section: Main Findings and Comparison With Previous Studiesmentioning

confidence: 99%

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Randomised comparison of growth hormone versus IGF-1 on early post-myocardial infarction ventricular remodelling in rats

Hatzistergos

Mitsi

Zachariou

et al. 2008

Growth Hormone & IGF Research

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“…In fact, pericardial administration of angiogenic growth factors and other cardioactive agents have shown beneficial effects in preclinical studies (17,18). In a porcine chronic myocardial ischemia model, the deposition of fibroblast growth factor in the pericardial sac induced functionally significant epicardial angiogenesis (18).…”

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confidence: 99%

Fused X-ray and MR Imaging Guidance of Intrapericardial Delivery of Microencapsulated Human Mesenchymal Stem Cells in Immunocompetent Swine

Fu¹,

Azene²,

Ehtiati

et al. 2014

Radiology

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Purpose To assess intrapericardial delivery of microencapsulated, xenogeneic human mesenchymal stem cells (hMSCs) by using x-ray fused with magnetic resonance (MR) imaging (x-ray/MR imaging) guidance as a potential treatment for ischemic cardiovascular disease in an immunocompetent swine model. Materials and Methods All animal experiments were approved by the institutional animal care and use committee. Stem cell microencapsulation was performed by using a modified alginate-poly-l-lysine-alginate encapsulation method to include 10% (wt/vol) barium sulfate to create barium-alginate microcapsules (BaCaps) that contained hMSCs. With x-ray/MR imaging guidance, eight female pigs (approximately 25 kg) were randomized to receive either BaCaps with hMSCs, empty BaCaps, naked hMSCs, or saline by using a percutaneous subxiphoid approach and were compared with animals that received empty BaCaps (n = 1) or BaCaps with hMSCs (n = 2) by using standard fluoroscopic delivery only. MR images and C-arm computed tomographic (CT) images were acquired before injection and 1 week after delivery. Animals were sacrificed immediately or at 1 week for histopathologic validation. Cardiac function between baseline and 1 week after delivery was evaluated by using a paired Student t test. Results hMSCs remained highly viable (94.8% ± 6) 2 days after encapsulation in vitro. With x-ray/MR imaging, successful intrapericardial access and delivery were achieved in all animals. BaCaps were visible fluoroscopically and at C-arm CT immediately and 1 week after delivery. Whereas BaCaps were free floating immediately after delivery, they consolidated into a pseudoepicardial tissue patch at 1 week, with hMSCs remaining highly viable within BaCaps; naked hMSCs were poorly retained. Follow-up imaging 1 week after x-ray/MR imaging–guided intrapericardial delivery showed no evidence of pericardial adhesion and/or effusion or adverse effect on cardiac function. In contradistinction, BaCaps delivery with xray fluoroscopy without x-ray/MR imaging (n = 3) resulted in pericardial adhesions and poor hMSC viability after 1 week. Conclusion Intrapericardial delivery of BaCaps with hMSCs leads to high cell retention and survival. With x-ray/MR imaging guidance, intrapericardial delivery can be performed safely in the absence of preexisting pericardial effusion to provide a novel route for cardiac cellular regenerative therapy.

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Intrapericardial IGF-I Improves Cardiac Function in an Ovine Model of Chronic Heart Failure

Cited by 17 publications

References 29 publications

Insulin-like growth factor-1 restores dexamethasone-induced heart growth arrest in rats: the role of the ubiquitin pathway

Insulin-like growth factor-1 restores dexamethasone-induced heart growth arrest in rats: the role of the ubiquitin pathway

Randomised comparison of growth hormone versus IGF-1 on early post-myocardial infarction ventricular remodelling in rats

Fused X-ray and MR Imaging Guidance of Intrapericardial Delivery of Microencapsulated Human Mesenchymal Stem Cells in Immunocompetent Swine

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