The delivery of angiogenic factors to the heart by microsphere therapy

Arras, Margarete; Mollnau, Hanke; Sträßer, Rudolf; Wenz, R.; Ito, Wulf; Schaper, Jutta; Schäper, Wolfgang

doi:10.1038/nbt0298-159

Cited by 57 publications

(30 citation statements)

References 16 publications

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“…Although therapeutic angiogenesis has been studied intensively as an alternative treatment for ischemic vascular diseases using growth factors such as VEGF, aFGF, bFGF or PDGF, these factors take a period of approximately 3 days to 3 weeks to act (1)(2)(3)(4)(5)(6)(7)(8), while myocardial necrosis in the acute severe coronary occlusion area occurs very rapidly within a matter of hours (4,(9)(10). The consequence is that fibrous tissue grows rapidly despite the relative ischemic condition, which replaces the infarcted heart tissues and also blocks the space for any newly-regenerated myocyte replacement.…”

Section: Introductionmentioning

confidence: 99%

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Gu¹,

Liu²

2006

Mol. Med.

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During remodeling progress post myocardial infarction, the contribution of neoangiogenesis to the infarct-bed capillary is insufficient to support the greater demands of the hypertrophied but viable myocardium resulting in further ischemic injury to the viable cardiomyocytes at risk. Here we reported the bio-assay-guided identification and isolation of angiogenic tannins (angio-T) from Geum japonicum that induced rapid revascularization of infarcted myocardium and promoted survival potential of the viable cardiomyocytes at risk after myocardial infarction. Our results demonstrated that angio-T displayed potent dual effects on up-regulating expression of angiogenic factors, which would contribute to the early revascularization and protection of the cardiomyocytes against further ischemic injury, and inducing antiapoptotic protein expression, which inhibited apoptotic death of cardiomyocytes in the infarcted hearts and limited infarct size. Echocardiographic studies demonstrated that angio-T-induced therapeutic effects on acute infarcted myocardium were accompanied by significant functional improvement by 2 days after infarction. This improvement was sustained for 14 days. These therapeutic properties of angio-T to induce early reconstitution of a blood supply network, prevent apoptotic death of cardiomyocytes at risk, and improve heart function post infarction appear entirely novel and may provide a new dimension for therapeutic angiogenesis medicine for the treatment of ischemic heart diseases.

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Section: Introductionmentioning

confidence: 99%

Untitled

Gu¹,

Liu²

2006

Mol. Med.

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“…The size of AGHMs is an important factor to achieve pinpoint delivery, because if the size of the AGHMs is too small, they pass through the capillary network and enter the venous system, 19 and if they are too large, they are likely to be trapped in more proximal branches, possibly worsening distal perfusion. 20 In the present study, we first determined the optimal size of AGHMs and then evaluated the function of the developed collateral vessels promoted by IA administration of bFGF-incorporating AGHMs.…”

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confidence: 99%

Gelatin Hydrogel Microspheres Enable Pinpoint Delivery of Basic Fibroblast Growth Factor for the Development of Functional Collateral Vessels

et al. 2004

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Background-Various growth factors promote collateral vessel development and are regarded as promising for the treatment of vascular occlusive diseases. However, an efficacious delivery system for them has yet to be established. We devised a strategy to augment functional collateral vessels by using acidic gelatin hydrogel microspheres (AGHMs) incorporating basic fibroblast growth factor (bFGF). The aim of the present study was to investigate the hypothesis that by intra-arterial (IA) administration of bFGF-impregnated AGHMs, bFGF could be delivered from AGHMs trapped in distal small-diameter vessels and thereby induce functional collateral vessels with an assured blood supply through the process of arteriogenesis. Methods and Results-Various sizes of AGHMs (3 mg) incorporating125 I-labeled bFGF were injected into the left internal iliac artery of a rabbit model of hindlimb ischemia. Less than 50% of radioactivity accumulated in the ischemic hindlimb after injection of AGHMs that were 10 m in diameter, whereas Ϸ80% of radioactivity was counted in the ischemic limb after administration of 29-or 59-m-diameter AGHMs. Calf blood pressure ratio and the ratio of regional blood flow of the bilateral hindlimbs immediately before and after IA administration of 29-m-diameter AGHMs showed no significant change. Then we evaluated the function of the developed collateral vessels 28 days after IA administration of bFGF-impregnated, 29-m-diameter AGHMs. IA administration of bFGF-impregnated AGHMs induced marked collateral vessel improvement compared with IA administration of phosphate buffered saline-treated AGHMs and intramuscular administration of bFGF-impregnated AGHMs.

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“…Microspheres injected via a coronary catheter has been used to deliver fibroblast growth factor (FGF). FGF was released from these microspheres and caused proliferation of endothelial cells (14). bFGF bound to platelets resembles this model.…”

Section: Discussionmentioning

confidence: 86%

ADP activation induces bFGF binding to platelets in vitro

Åkerblom

Lindahl

Larsson

2002

Upsala Journal of Medical Sciences

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Basic fibroblast growth factor (bFGF), is a heparin-binding factor with potent angiogenic properties in vitro and in vivo. bFGF is involved in tumour growth, but it has also been shown to reduce infarct size in experimentally induced acute myocardial infarction. Platelets are also believed to have an important role in both tumour growth and myocardial infarction.We have studied bFGF binding to platelets by flow cytometry. Platelet activation by ADP induces bFGF binding to platelets. bFGF bound to activated platelets will result in a locally high concentration of bFGF in patients with myocardial infarctions and malignant tumours. Addition of recombinant bFGF to platelet rich plasma reduced the percentage of fibrinogen positive platelets. bFGF may thus have an inhibitory effect on platelet aggregation.

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The delivery of angiogenic factors to the heart by microsphere therapy

Cited by 57 publications

References 16 publications

Untitled

Untitled

Gelatin Hydrogel Microspheres Enable Pinpoint Delivery of Basic Fibroblast Growth Factor for the Development of Functional Collateral Vessels

ADP activation induces bFGF binding to platelets in vitro

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