Hypoxic Preconditioning Triggers Myocardial Angiogenesis: a Novel Approach to Enhance Contractile Functional Reserve in Rat with Myocardial Infarction

Sasaki, Hiroaki; Fukuda, Shoji; Otani, Hajime; Zhu, Li; Yamaura, Genbu; Engelman, Richard M.; Das, Dipak K.; Maulik, Nilanjana

doi:10.1006/jmcc.2001.1516

Cited by 82 publications

(47 citation statements)

References 27 publications

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“…This report points out that enhanced level of VEGF may have some role in the inhibition of endothelial cell apoptosis. In our hypoxic preconditioned rat myocardial model, we have found cardiomyocyte apoptosis to be inversely proportional to VEGF expression [85] (Fig. 5).…”

Section: Hmi Vegf Mediated Angiogenesis Is Associated With Enhancmentioning

confidence: 60%

Potentiation of angiogenic response by ischemic and hypoxic reconditioning of the heart

Maulik

Das

2002

J Cellular Molecular Medi

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This review is intended to discuss the newly discovered role of preconditioning which should make it an attractive therapeutic stimulus for repairing the injured myocardium. We recently found that apart from rendering the myocardium tolerant to ischemic reperfusion injury, preconditioning also potentiates angiogenesis. Our study demonstrated for the first time that both ischemic and hypoxic preconditioning triggered myocardial angiogenesis at the capillary and arteriolar levels which nicely corroborated with the improved myocardial contractile function. Hypoxic preconditioning resulted in the stimulation of VEGF, the most potent angiogenic factor known to date. In concert, endothelial cell specific tyrosine kinase receptors, Tie 1, Tie 2 and Flt-1 and Flk-1 were also significantly enhanced in the preconditioned myocardium. The redox-regulated transcription factor NFkB was found to play an essential role in the preconditioning regulation of angiogenesis.

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Section: Hmi Vegf Mediated Angiogenesis Is Associated With Enhancmentioning

confidence: 60%

Potentiation of angiogenic response by ischemic and hypoxic reconditioning of the heart

Maulik

Das

2002

J Cellular Molecular Medi

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“…It is likely that the angiogenic response is only the beginning of a more powerful regeneration of vessels that will continue during days and weeks of recovery after HI, and that may be more pronounced after PC. Such a scenario is supported by a recent study in the heart showing that hypoxic PC 24 h before a period of ischemia triggered rapid angiogenesis and improved contractile function over a period of weeks (Sasaki et al, 2002). The enhanced density may contribute to alterations in the CBF (Klein et al, 1986) improving tissue oxygenation during HI.…”

Section: Discussionmentioning

confidence: 80%

Vascular Response to Hypoxic Preconditioning in the Immature Brain

Gustavsson

Mallard

Vannucci

et al. 2006

J Cereb Blood Flow Metab

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We hypothesized that hypoxic preconditioning (PC) modifies the microvasculature in the immature brain and thereby affects the cerebral blood flow (CBF) during a subsequent hypoxic-ischemic (HI) insult. On postnatal day 6 rats were exposed to hypoxia (361C, 8.0% O 2 ) or normoxia for 3 h. Unilateral HI (unilateral carotid ligation and 8% hypoxia) was induced 24 h later. Cortical CBF was measured with the 14 C-iodoantipyrine technique (at the end of HI) or with laser Doppler flowmetry (Perimed PF5001) before and during HI. At 0, 2, 8, and 24 h cerebral cortex was sampled and analyzed with gene arrays (Affymetrix 230 2.0). L-nitroarginine or vehicle was administrated before hypoxic PC or 30 mins before HI followed by CBF measurement (laser Doppler) during subsequent HI. Twenty-four hours after PC animals were perfusion-fixed and brains immunolabeled for von Willebrand factor and vascular density was determined by stereological quantification. The decrease in CBF during HI was attenuated significantly in PC versus control animals (P < 0.01), as detected by both techniques. Several vascular genes (Angpt2, Adm, Apln, Vegf, Flt1, Kdr, Pdgfra, Agtrap, Adora2a, Ednra, serpine1, caveolin, Id1, Prrx1, Ero1l, Acvrl1, Egfl7, Nudt6, Angptl4, Anxa2, and NOS3) were upregulated and a few (Csrp2, Adora2b) were downregulated after PC. A significant increase in vascular density (P < 0.05) was seen after PC. Nitric oxide synthase inhibition did not affect CBF during HI after PC. In conclusion, hypoxic PC upregulates vascular genes, increases vascular density and attenuates the decrease of CBF during a subsequent HI, which could contribute to tolerance.

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“…162 Angiogenesis is also stimulated by hypoxic preconditioning, which has been documented in the myocardium. 163 The therapeutic utility of this intervention is limited, given that hypoxic treatment must precede the ischemic stress. Alternatively, ectopic expression of the HIF-α subunits represents an attractive option.…”

Section: Monographsmentioning

confidence: 99%

Hypoxia-Induced Angiogenesis: Good and Evil

2011

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The vascular network delivers oxygen (O 2 ) and nutrients to all cells within the body. It is therefore not surprising that O 2 availability serves as a primary regulator of this complex organ. Most transcriptional responses to low O 2 are mediated by hypoxia-inducible factors (HIFs), highly conserved transcription factors that control the expression of numerous angiogenic, metabolic, and cell cycle genes. Accordingly, the HIF pathway is currently viewed as a master regulator of angiogenesis. HIF modulation could provide therapeutic benefit for a wide array of pathologies, including cancer, ischemic heart disease, peripheral artery disease, wound healing, and neovascular eye diseases. Hypoxia promotes vessel growth by upregulating multiple pro-angiogenic pathways that mediate key aspects of endothelial, stromal, and vascular support cell biology. Interestingly, recent studies show that hypoxia influences additional aspects of angiogenesis, including vessel patterning, maturation, and function. Through extensive research, the integral role of hypoxia and HIF signaling in human disease is becoming increasingly clear. Consequently, a thorough understanding of how hypoxia regulates angiogenesis through an ever-expanding number of pathways in multiple cell types will be essential for the identification of new therapeutic targets and modalities.

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Hypoxic Preconditioning Triggers Myocardial Angiogenesis: a Novel Approach to Enhance Contractile Functional Reserve in Rat with Myocardial Infarction

Cited by 82 publications

References 27 publications

Potentiation of angiogenic response by ischemic and hypoxic reconditioning of the heart

Potentiation of angiogenic response by ischemic and hypoxic reconditioning of the heart

Vascular Response to Hypoxic Preconditioning in the Immature Brain

Hypoxia-Induced Angiogenesis: Good and Evil

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