Analysis of angiogenesis induced by local IGF-1 expression after myocardial infarction using microSPECT-CT imaging

Dobrucki, Lawrence W.; Tsutsumi, Yoshio; Kalinowski, Leszek; Dean, Jarrod; Gavin, Mary; Sen, Sabyasachi; Mendizabal, Marivi; Sinusas, Albert J.; Aikawa, Ryuichi

doi:10.1016/j.yjmcc.2009.10.008

Cited by 65 publications

(58 citation statements)

References 39 publications

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“…Owing to the reported potent vascular IGF-1 effect [125], cardiomyocyte protection has been related to increased IGF-1-mediated angiogenesis, as assessed by microSPECT-CT (single-photon emission computed tomography-computed tomography) in adenovirusdelivered human IGF-1 gene models. In these models, a sustained IGF-1 expression in the peri-infarct area, reduced LV remodelling and improved cardiac function were also described [298]. Moreover, in injured muscle, IGF-1 has been shown to promote progenitor cell recruitment and to subsequently resolve the inflammatory response, thus enhancing local repair mechanisms [134].…”

Section: Atherosclerosis and MImentioning

confidence: 97%

IGF-1 and atherothrombosis: relevance to pathophysiology and therapy

et al. 2011

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IGF-1 (insulin-like growth factor-1) plays a unique role in the cell protection of multiple systems, where its fine-tuned signal transduction helps to preserve tissues from hypoxia, ischaemia and oxidative stress, thus mediating functional homoeostatic adjustments. In contrast, its deprivation results in apoptosis and dysfunction. Many prospective epidemiological surveys have associated low IGF-1 levels with late mortality, MI (myocardial infarction), HF (heart failure) and diabetes. Interventional studies suggest that IGF-1 has anti-atherogenic actions, owing to its multifaceted impact on cardiovascular risk factors and diseases. The metabolic ability of IGF-1 in coupling vasodilation with improved function plays a key role in these actions. The endothelial-protective, anti-platelet and anti-thrombotic activities of IGF-1 exert critical effects in preventing both vascular damage and mechanisms that lead to unstable coronary plaques and syndromes. The pro-survival and anti-inflammatory short-term properties of IGF-1 appear to reduce infarct size and improve LV (left ventricular) remodelling after MI. An immune-modulatory ability, which is able to suppress 'friendly fire' and autoreactivity, is a proposed important additional mechanism explaining the anti-thrombotic and anti-remodelling activities of IGF-1. The concern of cancer risk raised by long-term therapy with IGF-1, however, deserves further study. In the present review, we discuss the large body of published evidence and review data on rhIGF-1 (recombinant human IGF-1) administration in cardiovascular disease and diabetes, with a focus on dosage and safety issues. Perhaps the time has come for the regenerative properties of IGF-1 to be assessed as a new pharmacological tool in cardiovascular medicine.

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Section: Atherosclerosis and MImentioning

confidence: 97%

IGF-1 and atherothrombosis: relevance to pathophysiology and therapy

et al. 2011

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“…The high-sensitivity images obtained with singlephoton emission tomography and positron emission tomography can now be colocalized with high-resolution x-ray CT anatomical images to better identify and quantify radiotracer uptake within the cardiovascular system with the availability of hybrid imaging systems. Radiotracer imaging, including hybrid single-photon emission tomography/CT approaches, has been applied to evaluate angiogenesis and arteriogenesis in rodent models of hind-limb ischemia 218 and myocardial ischemia, 187 as well as in larger canine and porcine models of ischemia-induced angiogenesis. 185,186 Figure 8 illustrates the integration of physiological perfusion imaging and targeted molecular imaging of angiogenesis using hybrid singlephoton emission tomography/CT imaging in a murine model of hind-limb ischemia and the application of serial perfusion imaging for the evaluation of angiogenesis in a porcine model of hind-limb ischemia.…”

mentioning

confidence: 99%

State-of-the-Art Methods for Evaluation of Angiogenesis and Tissue Vascularization

Simons¹,

Alitalo²,

Annex³

et al. 2015

Circulation Research

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114

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“…These beneficial effects have been attributed to Akt induced myocyte survival through an anti-apoptotic effect 18 , angiogenesis 19 and the protection of resident progenitor stem cells in the heart 20 . These data indicate that a single, systemic injection of H-IGF1 is able to preserve cardiac function and limit the development of cardiac fibrosis following MI.…”

Section: Discussionmentioning

confidence: 99%

Targeting extracellular DNA to deliver IGF-1 to the injured heart

Khan

Brown

et al. 2013

Cardiovascular Pathology

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There is a great need for the development of therapeutic strategies that can target biomolecules to damaged myocardium. Necrosis of myocardium during a myocardial infarction (MI) is characterized by extracellular release of DNA, which can serve as a potential target for ischemic tissue. Hoechst, a histological stain that binds to double-stranded DNA can be conjugated to a variety of molecules. Insulin-like growth factor-1 (IGF-1), a small protein/polypeptide with a short circulating-half life is cardioprotective following MI but its clinical use is limited by poor delivery, as intra-myocardial injections have poor retention and chronic systemic presence has adverse side effects. Here, we present a novel delivery vehicle for IGF-1, via its conjugation to Hoechst for targeting infarcted tissue. Using a mouse model of ischemia-reperfusion, we demonstrate that intravenous delivery of Hoechst-IGF-1 results in activation of Akt, a downstream target of IGF-1 and protects from cardiac fibrosis and dysfunction following MI. D espite significant advances in therapy, a substantial proportion of patients treated for myocardial infarction (MI) develop congestive heart failure 1 . Recent breakthroughs in regenerative medicine with cell and growth factor based therapies show tremendous potential in reducing this risk. Current pharmacologic and device therapies however do not target damaged myocardium or recover functional myocardium, and rather serve to boost cardiac function and reduce inflammation. As damage from MI is mainly regional, localized therapy holds the most promise 2 . Growth factor based therapeutics have shown great potential in regenerating the heart 3 . Insulin-like growth factor-1 (IGF-1) has demonstrated a cardio-protective and regenerative effect on the myocardium 4 . These benefits are primarily ascribed to the short-term actions of IGF-1 via activation of pro-survival pathways such as those mediated via Akt. In contrast, chronic exposure may be deleterious, associated with the development of pathologic cardiac hypertrophy and cancer 5,6 . Regulating the temporal effects of IGF-1 has been challenging, in part by its short circulating half-life, which has required prolonged infusions of growth hormone to raise IGF-1 levels, and its small size (,9 kDa), which results in poor tissue retention following direct injection 7 . For example, direct delivery of free IGF-1 to the infarcted heart does not allow for sufficient retention and does not lead to any improvement in cardiac function 7 . Thus, finding new ways to acutely localize IGF-1 delivery to the damaged myocardium could maximize its therapeutic benefits.During an acute MI, excessive necrosis releases DNA in to the extracellular space. Given that nearly ten million cells show compromised cell membranes in rat models of MI 8 this could mean on the order of picograms of DNA per cardiac cell. With estimates that scale rat to human studies demonstrating billions of myocytes potentially undergoing necrosis following acute MI, this represents a significant clin...

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Analysis of angiogenesis induced by local IGF-1 expression after myocardial infarction using microSPECT-CT imaging

Cited by 65 publications

References 39 publications

IGF-1 and atherothrombosis: relevance to pathophysiology and therapy

IGF-1 and atherothrombosis: relevance to pathophysiology and therapy

State-of-the-Art Methods for Evaluation of Angiogenesis and Tissue Vascularization

Targeting extracellular DNA to deliver IGF-1 to the injured heart

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