Differential involvement of MMP-2 and VEGF during  muscle stretch- versus shear stress-induced angiogenesis

Rivilis, Irina; Milkiewicz, Małgorzata; Boyd, Pamela J.; Goldstein, Jason; Brown, Margaret D.; Egginton, Stuart; Hansen, Fay M.; Hudlická, O; Haas, Tara L.

doi:10.1152/ajpheart.00082.2002

Cited by 150 publications

(202 citation statements)

References 56 publications

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“…It is notable that VEGF-A protein levels are elevated after 2 days of prazosin treatment (Milkiewicz et al, 2001;Rivilis et al, 2002). We observed substantial increases in VEGF-A protein levels in response to shear stress stimulation in vitro, which were abrogated by inhibition of p38 activity.…”

Section: Discussionmentioning

confidence: 61%

“…Shear stress-induced angiogenesis does not involve basement membrane degradation (Rivilis et al, 2002). We reported previously that basement membrane degrading enzyme, matrix metalloproteinase-2 (MMP-2), is downregulated by shear stress in a p38 dependent manner (Milkiewicz et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies reported that elevated shear stress causes increased VEGF production (Milkiewicz et al, 2001;Rivilis et al, 2002). We assessed the role of p38 in VEGF protein production in response to shear stress.…”

Section: The Role Of P38 In Shear Stress-mediated Vegf Productionmentioning

confidence: 99%

“…The additional flow path may reduce shear stress through the capillary network and provide improved oxygen delivery. Luminal splitting occurs in the absence of significant endothelial cell proliferation or basement membrane degradation (Rivilis et al, 2002). However, cellular signals needed for luminal splitting are not well characterized.…”

Section: Introductionmentioning

confidence: 99%

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p38 MAPK activity is stimulated by vascular endothelial growth factor receptor 2 activation and is essential for shear stress‐induced angiogenesis

Gee

Milkiewicz

Haas

2009

Journal Cellular Physiology

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Increased capillary shear stress induces angiogenesis in skeletal muscle, but the signaling mechanisms underlying this response are not known. We hypothesize that shear stress-dependent activation of vascular endothelial growth factor receptor 2 (VEGFR2) causes p38 and ERK1/2 phosphorylation, which contribute to shear stress-induced angiogenesis. Skeletal muscle microvascular endothelial cells were sheared (12 dynes/cm 2 , 0.5-24 hours). VEGFR2-Y1214 phosphorylation increased in response to elevated shear stress and VEGF stimulation. p38 and ERK1/2 phosphorylation increased at 2 hours of shear stress, but only p38 remained phosphorylated at 6 and 24 hours of shear stress. VEGFR2 inhibition abrogated p38, but not ERK1/2 phosphorylation. VEGF production was increased in response to shear stress at 6 hours, and this increased production was abolished by p38 inhibition. Male Sprague-Dawley rats were administered prazosin (50 mg/L drinking water, 1, 2, 4 or 7 days) to induce chronically elevated capillary shear stress in skeletal muscle. In some experiments, mini-osmotic pumps were used to dispense p38 inhibitor SB203580 or its inactive analog SB202474, to the extensor digitorum longus (EDL) of control and prazosin treated rats. Immunostaining and Western blotting showed increases in p38 phosphorylation in capillaries from rats treated with prazosin for 2 days but returned to basal levels at 4 and 7 days. p38 inhibition abolished the increase in capillary to muscle fibre ratio seen after 7 days of prazosin treatment. Our data suggest that p38 activation is necessary for shear stress-dependent angiogenesis.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: The Role Of P38 In Shear Stress-mediated Vegf Productionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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p38 MAPK activity is stimulated by vascular endothelial growth factor receptor 2 activation and is essential for shear stress‐induced angiogenesis

Gee

Milkiewicz

Haas

2009

Journal Cellular Physiology

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“…A rise in VEGF expression is reported within the first few days of prazosin treatment, followed by a reduction in protein levels after 4 weeks (Rivilis et al . 2002, Egginton et al . 2011).…”

Section: Discussionmentioning

confidence: 99%

Shear stress‐induced angiogenesis in mouse muscle is independent of the vasodilator mechanism and quickly reversible

et al. 2016

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AimIs modulation of skeletal muscle capillary supply by altering blood flow due to a presumptive shear stress response per se, or dependent on the vasodilator mechanism?MethodsThe response to four different vasodilators, and cotreatment with blockers of NO and prostaglandin synthesis, was compared. Femoral artery blood flow was correlated with capillary‐to‐fibre ratio (C:F) and protein levels of putative angiogenic compounds.ResultsAll vasodilators induced a similar increase in blood flow after 14 days, with a similar effect on C:F (1.62 ± 0.05, 1.60 ± 0.01, 1.57 ± 0.06, 1.57 ± 0.07, respectively, all P < 0.05 vs. control 1.20 ± 0.01). Concomitant inhibitors revealed differential effects on blood flow and angiogenesis, demonstrating that a similar response may have different signalling origins. The time course of this response with the most commonly used vasodilator, prazosin, showed that blood flow increased from 0.40 mL min−1 to 0.61 mL min−1 by 28 days (P < 0.05), dropped within 1 week after the cessation of treatment (0.54 mL min−1; P < 0.05) and returned to control levels by 6 weeks. In parallel with FBF, capillary rarefaction began within 1 week (P < 0.05), giving C:F values similar to control by 2 weeks. Of the dominant signalling pathways, prazosin decreased muscle VEGF, but increased its cognate receptor Flk‐1 (both P < 0.01); levels of eNOS varied with blood flow (P < 0.05), and Ang‐1 initially increased, while its receptor Tie‐2 was unchanged, with only modest changes in the antiangiogenic factor TSP‐1.ConclusionHyperaemia‐induced angiogenesis, likely in response to elevated shear stress, is independent of the vasodilator involved, with a rapid induction and quick regression following the stimulus withdrawal.

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The response of human embryonic stem cell‐derived endothelial cells to shear stress

Metallo

Vodyanik

Pablo

et al. 2008

Biotech & Bioengineering

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An important physiological function of vascular endothelial cells is to detect and respond to physical stimuli. While many efforts have been made to derive endothelial cells from human embryonic stem cells (hESCs), the ability of these derivatives to respond to mechanical forces has yet to be ascertained. hESC-derived endothelial cells (hEECs) were obtained by coculturing hESCs with OP9 stromal cells. Here we applied physiologic levels of shear stress to hEECs in a parallel plate flow chamber and observed changes in cell morphology and gene expression, comparing the response to that of human umbilical vein endothelial cells (HUVECs) and human microvascular endothelial cells (HMVECs). Shear induced hEECs to elongate and align in the direction of flow, and their overall transcriptional response to shear was similar to the primary cells tested. In response to shear in hEECs, COX2 and MMP1 were upregulated four- and threefold, MCP1 and VCAM1 expression decreased over fivefold, and ICAM1 and TPA were downregulated almost threefold. TGFbeta1 and SOD2 transcription exhibited no change under the conditions tested. Additionally, preshearing of hEECs mitigated TNFalpha-induced VCAM1 surface expression. These findings suggest that hEECs are capable of functionally responding to changes in fluid shear stress by modulating gene expression and cell morphology.

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Differential involvement of MMP-2 and VEGF during muscle stretch- versus shear stress-induced angiogenesis

Abstract: . Differential involvement of MMP-2 and VEGF during muscle stretch-versus shear stress-induced angiogenesis.

Cited by 150 publications

References 56 publications

p38 MAPK activity is stimulated by vascular endothelial growth factor receptor 2 activation and is essential for shear stress‐induced angiogenesis

p38 MAPK activity is stimulated by vascular endothelial growth factor receptor 2 activation and is essential for shear stress‐induced angiogenesis

Shear stress‐induced angiogenesis in mouse muscle is independent of the vasodilator mechanism and quickly reversible

The response of human embryonic stem cell‐derived endothelial cells to shear stress

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