Early Expression of Angiogenesis Factors in Acute Myocardial Ischemia and Infarction

Lee, Sang H.; Wolf, Paul L.; Escudero, Ryan; Deutsch, Reena; Jamieson, Stuart W.; Thistlethwaite, Patricia A.

doi:10.1056/nejm200003023420904

Cited by 631 publications

(452 citation statements)

References 40 publications

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“…[9][10][11][12] EPCs are characterized by CD34, Flk-1, and CD133 antigen-positive cells, 13,14 and these cells are localized predominantly in the bone marrow. 15 In the peripheral circulation of adults, more mature, differentiated EPCs are found that are characterized by a decreased expression of CD133, are positive for VEGFR-2, and still express CD34.…”

Section: Introductionmentioning

confidence: 99%

Involvement of circulating endothelial progenitor cells and vasculogenic factors in the pathogenesis of diabetic retinopathy

Lee

Chae

Kim

2005

Eye

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Section: Introductionmentioning

confidence: 99%

Involvement of circulating endothelial progenitor cells and vasculogenic factors in the pathogenesis of diabetic retinopathy

Lee

Chae

Kim

2005

Eye

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“…Endogenous angiogenic factors, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2), are naturally produced in response to tissue hypoxia and during wound healing. [1][2][3] This restorative process is, however, often insufficient to prevent tissue ischemia and necrosis, due in part to the slow kinetics and inadequate secretion of growth factors. Exogenous delivery of either VEGF or FGF-2 by single bolus injection has proven to be efficacious in stimulating localized angiogenesis and improving blood circulation in animal models of myocar-the distal, ischemic region of the flap.…”

Section: Introductionmentioning

confidence: 99%

Delivery of FGF-2 but not VEGF by encapsulated genetically engineered myoblasts improves survival and vascularization in a model of acute skin flap ischemia

et al. 2001

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Stimulating angiogenesis by gene transfer approaches offers the hope of treating tissue ischemia which is untreatable by currently practiced techniques of vessel grafting and bypass surgery. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) are potent angiogenic molecules, making them ideal candidates for novel gene transfer protocols designed to promote new blood vessel growth. In this study, an ex vivo gene therapy approach utilizing cell encapsulation was employed to deliver VEGF and FGF-2 in a continuous and localized manner. C(2)C(12) myoblasts were genetically engineered to secrete VEGF(121), VEGF(165) and FGF-2. These cell lines were encapsulated in hollow microporous polymer membranes for transplantation in vivo. Therapeutic efficacy was evaluated in a model of acute skin flap ischemia. Capsules were positioned under the distal, ischemic region of the flap. Control flaps showed 50% necrosis at 1 week. Capsules releasing either form of VEGF had no effect on flap survival, but induced a modest increase in distal vascular supply. Delivery of FGF-2 significantly improved flap survival, reducing necrosis to 34.2% (P < 0.001). Flap vascularization was significantly increased by FGF-2 (P < 0.01), with numerous vessels, many of which had a large lumen diameter, growing in the proximity of the implanted capsules. These results demonstrate that FGF-2, delivered from encapsulated cells, is more efficacious than either VEGF(121) or VEGF(165) in treating acute skin ischemia and improving skin flap survival. Furthermore, these data attest to the applicability of cell encapsulation for the delivery of angiogenic factors for the treatment and prevention of tissue ischemia

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“…Several studies have found increased expression of HIF-α messenger RNA (mRNA) in hypoxic cultured cells and in organs (the retina and the lung) of animals exposed to short-term or long-term hypoxia [8,9]. Moreover, an early increase in the cardiac expression of HIF-1α has been observed in response to myocardial ischaemia or infarction in humans [10].…”

mentioning

confidence: 99%

Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size and early expression of hypoxia-inducible factor 1

et al. 2002

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Aims/hypothesis. This study aimed to evaluate the effects of hyperglycaemia on the evolution of myocardial infarction and the expression of the transcriptional factor for angiogenesis hypoxia-inducible factor 1α (HIF-1α) in the rat. Methods. We studied the effects of streptozotocin induced diabetes on infarct size and HIF-1α gene expression. These parameters were also evaluated in isolated hearts of non-diabetic rat, in condition of high glucose concentration. Results. In streptozotocin (STZ)-diabetic rats (in vivo study), myocardial infarct size was greater (p<0.01) in hyperglycaemic rats (22 mmol/l) than in normoglycaemic (7 mmol/l) or non-diabetic rats. In euglycaemic conditions, basal expression of HIF-1α mRNA was not appreciable, but increased steadily after ischaemia (762±86%, p<0.001); this response was blunted in hyperglycaemic STZ-rats (6.8±6% of the control, p<0.001) and improved in euglycaemic STZ-rats (58±10%). The changes in myocardial Rac1 mRNA expression paralleled those of HIF-1α. In isolated hearts from non-diabetic rats (in vitro study), perfusion with high glucose (33 mmol/l) produced an infarct size (58±2% of the area at risk) not different from that obtained in hyperglycaemic STZ-rats (57±2%). Similar changes in the expression of HIF-1α and Rac1, which were prevented by glutathione infusion (0.3 mmol/l) were also observed. Conclusion/interpretation. Both hyperglycaemia and high glucose concentrations increased basal HIF-1α and Rac1 expression, suggesting a state of pseudohypoxia. These findings show that myocardial infarct size in the rat is increased in hyperglycaemic conditions and is associated with a reduced expression of the HIF-1α gene. These changes are reversed, totally or partially, by normoglycaemia or glutathione suggesting a role for reactive oxygen species generation brought about by hyperglycaemia. [Diabetologia (2002[Diabetologia ( ) 45:1172[Diabetologia ( -1181

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Early Expression of Angiogenesis Factors in Acute Myocardial Ischemia and Infarction

Cited by 631 publications

References 40 publications

Involvement of circulating endothelial progenitor cells and vasculogenic factors in the pathogenesis of diabetic retinopathy

Involvement of circulating endothelial progenitor cells and vasculogenic factors in the pathogenesis of diabetic retinopathy

Delivery of FGF-2 but not VEGF by encapsulated genetically engineered myoblasts improves survival and vascularization in a model of acute skin flap ischemia

Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size and early expression of hypoxia-inducible factor 1

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