Unorthodox angiogenesis in skeletal muscle

Egginton, Stuart; Zhang, Ailing; Brown, Margaret D.; Hudlická, O

doi:10.1016/s0008-6363(00)00282-0

Cited by 194 publications

(247 citation statements)

References 29 publications

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“…It should be noted, however, that a difference between the present model and the above-described rodent model, used to study the role of mechanical stretch in angiogenesis (9), is that the present model is not paralleled by mechanical overload, and therefore the impact of stretch is likely to be smaller.…”

mentioning

confidence: 89%

Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle

Hellsten¹,

Rufener²,

Nielsen³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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The present study used passive limb movement as an experimental model to study the effect of increased blood flow and passive stretch, without enhanced metabolic demand, in young healthy male subjects. The model used was 90 min of passive movement of the leg leading to a 2.8-fold increase ( P < 0.05) in blood flow without a significant enhancement in oxygen uptake. Muscle interstitial fluid was sampled with microdialysis technique and analyzed for vascular endothelial growth factor (VEGF) protein and for the effect on endothelial cell proliferation. Biopsies obtained from the musculus vastus lateralis were analyzed for mRNA content of VEGF, endothelial nitric oxide synthase (eNOS), and matrix metalloproteinase-2 (MMP-2). The passive leg movement caused an increase ( P < 0.05) in interstitial VEGF protein concentration above rest (73 ± 21 vs. 344 ± 83 pg/ml). Addition of muscle dialysate to cultured endothelial cells revealed that dialysate obtained during leg movement induced a 3.2-fold higher proliferation rate ( P < 0.05) than dialysate obtained at rest. Passive movement also enhanced ( P < 0.05) the eNOS mRNA level fourfold above resting levels. VEGF mRNA and MMP-2 mRNA levels were unaffected. The results show that a session of passive leg movement, elevating blood flow and causing passive stretch, augments the interstitial concentrations of VEGF, the proliferative effect of interstitial fluid, and eNOS mRNA content in muscle tissue. We propose that enhanced blood flow and passive stretch are positive physiological stimulators of factors associated with capillary growth in human muscle.

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mentioning

confidence: 89%

Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle

Hellsten¹,

Rufener²,

Nielsen³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…One mechanism by which MVs evolve into capillaries involves intraluminal bridging, a process that was originally discovered in tumour vessels (Nagy et al, 1995), but which has since been found to occur in the angiogenesis induced by Ad-VEGF-A 164 (Pettersson et al, 2000) and healing wounds (Ren et al, 2002), and after chronic vascular dilatation (Egginton et al, 2001). Endothelial cells extend cytoplasmic processes into and across MV lumens, forming transluminal bridges that divide blood flow into multiple smaller-sized channels.…”

Section: Capillariesmentioning

confidence: 99%

Why are tumour blood vessels abnormal and why is it important to know?

et al. 2009

Br J Cancer

513

425

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Tumour blood vessels differ from their normal counterparts for reasons that have received little attention. We report here that they are of at least six distinct types, we describe how each forms, and, looking forward, encourage the targeting of tumour vessel subsets that have lost their vascular endothelial growth factor-A (VEGF-A) dependency and so are likely unresponsive to anti-VEGF-A therapies.

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“…It has been reported that during the early stages of neovascularization, leading sprouts consisting of collagen IV basement membrane can be observed before endothelial cell proliferation and migration. [35][36][37] To determine whether these sprouts existed in the omentum, immune aggregates and their associated vasculature were identified as before ( Figure 4A, overlay of immune cells in red, and blood vessels in green) and stained simultaneously with anticollagen IV to highlight sprouts ( Figure 4, B and C). In Figure 4B, collagen is observed sheathing most vessels in the aggregate.…”

Section: The Unique Phenotype Of the Blood Vasculature Of The Omentummentioning

confidence: 99%

Preferential Attachment of Peritoneal Tumor Metastases to Omental Immune Aggregates and Possible Role of a Unique Vascular Microenvironment in Metastatic Survival and Growth

Gerber

Rybalko

Bigelow

et al. 2006

The American Journal of Pathology

169

157

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Controlling metastases remains a critical problem in cancer biology. Within the peritoneal cavity, omental tissue is a common site for metastatic disease arising from intraperitoneal tumors; however, it is unknown why this tissue is so favorable for metastatic tumor growth. Using five different tumor cell lines in three different strains of mice, we found that the omentum was a major site of metastases growth for intraperitoneal tumors. Furthermore, initial attachment and subsequent growth were limited to specific sites within the omentum, consisting of organized aggregates of immune cells. These immune aggregates contained a complex network of capillaries exhibiting a high vascular density, which appear to contribute to the survival of metastatic cells. We found that the vasculature within these aggregates contained CD105؉ vessels and vascular sprouts, both indicators of active angiogenesis. A subset of mesothelial cells situated atop the immune aggregates was found to be hypoxic, and a similar proportion was observed to secrete vascular endothelial growth factor-A. These data provide a physiological mechanism by which metastatic tumor cells preferentially grow at sites rich in proangiogenic vessels, apparently stimulated by angiogenic factors produced by mesothelial cells. These sites provide metastatic cells with a microenvironment highly conducive to survival and subsequent growth.

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Unorthodox angiogenesis in skeletal muscle

Cited by 194 publications

References 29 publications

Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle

Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle

Why are tumour blood vessels abnormal and why is it important to know?

Preferential Attachment of Peritoneal Tumor Metastases to Omental Immune Aggregates and Possible Role of a Unique Vascular Microenvironment in Metastatic Survival and Growth

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