Therapeutic angiogenesis with intramyocardial administration of basic fibroblast growth factor

Kawasuji, Michio; Nagamine, Hiroshi; Ikeda, Masahiro; Sakakibara, Naoki; Takemura, Hirofumi; Fujii, Susumu; Watanabe, Yoh

doi:10.1016/s0003-4975(99)01557-x

Cited by 48 publications

(32 citation statements)

References 20 publications

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“…4 However, angiogenesis induced by growth factors has not been always successful. Despite high binding affinity for acidic polysaccharides such as heparin and heparan sulfate in the extracellular matrix, bFGF has a short biological half-life in tissues.…”

Section: Circulation Journal Vol70 April 2006mentioning

confidence: 99%

Effects of Intramyocardial Administration of Slow-Release Basic Fibroblast Growth Factor on Angiogenesis and Ventricular Remodeling in a Rat Infarct Model

Shao

Takaji

Katayama

et al. 2006

Circ J

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oth coronary artery bypass grafting and percutaneous coronary intervention ameliorate angina pectoris, prevent myocardial infarction and improve the long-term survival of patients with atherosclerotic coronary artery disease. However, the nature of coronary arteries significantly impacts the quality of life. Standard therapies for myocardial revascularization are often limited because of diffuse lesions or small-caliber vessels. Angiogenic therapy to induce myocardial neovascularization is not dependent on vessel caliber and provides an alternative treatment alone or in combination with standard revascularization. Basic fibroblast growth factor (bFGF) is a potent angiogenic protein that induces endothelial and smooth muscle cell proliferation in vivo and elicits angiogenesis that includes the migration and proliferation of endothelial cells, vascular tube formation and linkage to the extant vascular network. 1 Intracoronary injections of bFGF reduce infarct size in a canine model of myocardial infarction and improve myocardial function in chronically ischemic porcine hearts. 2,3 We have previously shown that the intramyocardial administration of bFGF increased the number of capillaries and arterioles in the peri-infarct region, increased regional myocardial blood flow and consequently improved ven- Circulation Journal Vol.70, April 2006tricular function in a canine infarction model. 4 However, angiogenesis induced by growth factors has not been always successful. Despite high binding affinity for acidic polysaccharides such as heparin and heparan sulfate in the extracellular matrix, bFGF has a short biological half-life in tissues. 5 The sustained release of bFGF might help to enhance its angiogenic activity in vivo. 6,7 Gelatin is a nontoxic, biodegradable, natural polymer with low antigenicity and gelatin hydrogel is considered to be a preferable matrix for the sustained release of protein drugs, such as growth factors. 8,9 However, the effects of intramyocardial injections of slow-release bFGF on vascular growth, cardiomyocyte apoptosis and cardiac function have not been investigated in detail. The present study evaluates the ability of gelatin hydrogels to enhance the benefits of bFGF on neoangiogenesis, cardiomyocyte apoptosis, myocardial fibrosis, ventricular remodeling and cardiac function in a rat infarction model. Methods Preparation of bFGFHuman recombinant bFGF and gelatin hydrogels were provided by Kaken Pharmaceutical, Tokyo, Japan. Gelatin with an isoelectric point of 4.9 was prepared using alkaline treatment of bovine collagen with Ca(OH)2. To obtain gelatin hydrogels that incorporated bFGF, 0.7 ml of saline containing 350 g of bFGF was impregnated into freezedried hydrogels. The release of biologically active bFGF is sustained as a result of hydrogel degradation in vivo. Empty gelatin hydrogels free of bFGF were similarly prepared. Background Basic fibroblast growth factor (bFGF) stimulates neoangiogenesis. Incorporation into biodegradable gelatin hydrogels provides the sustained release of bFGF....

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Section: Circulation Journal Vol70 April 2006mentioning

confidence: 99%

Effects of Intramyocardial Administration of Slow-Release Basic Fibroblast Growth Factor on Angiogenesis and Ventricular Remodeling in a Rat Infarct Model

Shao

Takaji

Katayama

et al. 2006

Circ J

Self Cite

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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%

Untitled

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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“…13,14,27,28) We and other groups have confirmed that supplementation or over-expression of FGFs can protect the heart from ischemia/reperfusion (I/R)-induced injury in animal models and in patients. [29][30][31][32][33][34][35][36] However, whether FGFs can protect diabetic heart from I/Rinduced injury has not been addressed.…”

mentioning

confidence: 99%

Cardiac Protection by Basic Fibroblast Growth Factor from Ischemia/Reperfusion-Induced Injury in Diabetic Rats

Xiao

Lin

et al. 2010

Biological & Pharmaceutical Bulletin

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Diabetes impairs the expression and function of endogenous growth factors, leading to increased cardiovascular events in diabetic patients. Supplementation of fibroblast growth factors (FGFs) protected the heart from ischemia/reperfusion (I/R)-induced injury in animal models. However, it has not yet been tested in diabetic heart. The present study was thus to clarify whether basic fibroblast growth factor (bFGF) could protect the heart from I/R-induced damage under diabetic conditions using a rat model. Male Sprague Dawley rats were used to induce diabetes by intraperitoneal injection of streptozotocin. Eight weeks later, I/R injury was generated in diabetic rats and age-matched non-diabetic rats. All I/R rats were administrated bFGF or saline through intramyocardial injection. Seven days after I/R, cardiac infarction, structural changes, cell death and blood vessel density, serum malondialdehyde (MDA) and cardiac enzyme lactate dehydrogenase (LDH) were examined. We found that I/R induced significant increases in the cardiac infarction, blood MDA contents and LDH activities, and the expression of caspase-3. Treatment of I/R rats with bFGF simultaneously with reperfusion significantly attenuated I/Rinduced pathological changes, along with a significant increase in the cardiac blood vessel density in both diabetic and non-diabetic rates. The protective effects of bFGF on I/R-induced cardiac injury in diabetic group are less than those in non-diabetic group. The results indicated that bFGF provide a protection of the heart against I/R-induced oxidative damage, cell death and infarction under diabetic conditions.

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Therapeutic angiogenesis with intramyocardial administration of basic fibroblast growth factor

Cited by 48 publications

References 20 publications

Effects of Intramyocardial Administration of Slow-Release Basic Fibroblast Growth Factor on Angiogenesis and Ventricular Remodeling in a Rat Infarct Model

Effects of Intramyocardial Administration of Slow-Release Basic Fibroblast Growth Factor on Angiogenesis and Ventricular Remodeling in a Rat Infarct Model

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Cardiac Protection by Basic Fibroblast Growth Factor from Ischemia/Reperfusion-Induced Injury in Diabetic Rats

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