Phosphorylation of murine double minute‐2 on Ser
            166
            is downstream of VEGF‐A in exercised skeletal muscle and regulates primary endothelial cell migration and
            FoxO
            gene expression

The role of angiotensin II (ANG II) in postnatal vasculogenesis and angiogenesis during skeletal muscle (SKM) regeneration is unknown. We examined the capacity of ANG II to stimulate capillary formation and growth during cardiotoxin-induced muscle regeneration in ACE inhibitor-treated ANG II type 1a receptor knockout (AT1a−/−) and C57Bl/6 control mice. Analysis of tibialis anterior (TA) cross-sections revealed 17% and 23% reductions in capillarization in AT1a−/− and captopril treated mice, respectively, when compared with controls, 21 days postinjury. Conversely, no differences in capillarization were detected at early time points (7 and 10 days). These results identify ANG II as a regulator of angiogenesis but not vasculogenesis in vivo. In vitro angiogenesis assays of human umbilical vein endothelial cells (HUVECs) further confirmed ANG II as proangiogeneic as 71% and 124% increases in tube length and branch point number were observed following ANG II treatment. Importantly, treatment of HUVECs with conditioned media from differentiated muscle cells resulted in an 84% and 203% increase in tube length and branch point number compared with controls, which was abolished following pretreatment of the cells with an angiotensin-converting enzyme inhibitor. The pro-angiogenic effect of ANG II can be attributed to an enhanced endothelial cell migration because both transwell and under agarose migration assays revealed a 37% and 101% increase in cell motility, respectively. Collectively, these data highlight ANG II as a proangiogenic regulator during SKM regeneration in vivo and more importantly demonstrates that ANG II released from SKM can signal endothelial cells and regulate angiogenesis through the induction of endothelial cell migration.

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CaMKIIδ Is Necessary for Endothelial Cell Migration and Regulates Spouting Angiogenesis through Modification of MEF2‐dependent Gene Expression

The FASEB Journal ◽

10.1096/fasebj.2020.34.s1.03277 ◽

2020 ◽

Vol 34 (S1) ◽

pp. 1-1 ◽

Cited By ~ 1

Author(s):

Brendan J. O’Brien ◽

Roman G. Ginnan ◽

Harold A. Singer

Keyword(s):

Gene Expression ◽

Cell Migration ◽

Endothelial Cell ◽

Endothelial Cell Migration

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The histone methyltransferase MLL is an upstream regulator of endothelial-cell sprout formation

Blood ◽

10.1182/blood-2006-08-039651 ◽

2006 ◽

Vol 109 (4) ◽

pp. 1472-1478 ◽

Cited By ~ 46

Author(s):

Florian Diehl ◽

Lothar Rössig ◽

Andreas M. Zeiher ◽

Stefanie Dimmeler ◽

Carmen Urbich

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Cell Migration ◽

Endothelial Cell ◽

Umbilical Vein ◽

Underlying Mechanism ◽

Endothelial Cell Migration ◽

Cell Functions ◽

Sprout Formation

Abstract Posttranslational histone modification by acetylation or methylation regulates gene expression. Here, we investigated the role of the histone lysine methyltransferase MLL for angiogenic functions in human umbilical vein endothelial cells. Suppression of MLL expression by siRNA or incubation with the pharmacologic methyltransferase inhibitor 5′-deoxy-5′-(methylthio)adenosine significantly decreased endothelial-cell migration and capillary sprout formation, indicating that methyltransferase activity is required for proangiogenic endothelial-cell functions. Because the expression of homeodomain transcription factors (Hox) is regulated by MLL, we elucidated the role of Hox gene expression. MLL silencing was associated with reduced mRNA and protein expression of HoxA9 and HoxD3, whereas HoxB3, HoxB4, HoxB5, and HoxB9 were not altered. Overexpression of HoxA9 or HoxD3 partially compensated for impaired migration in MLL siRNA-transfected endothelial cells, suggesting that HoxA9 and HoxD3 both contribute to MLL-dependent migration. As a potential underlying mechanism, MLL siRNA down-regulated mRNA and protein levels of the HoxA9-dependent axon guidance factor EphB4. In contrast, MLL knockdown effects on capillary sprouting were not rescued by HoxA9 or HoxD3 overexpression, indicating that MLL affects additional targets required for 3-dimensional sprout formation. We conclude that MLL regulates endothelial-cell migration via HoxA9 and EphB4, whereas sprout formation requires MLL-dependent signals beyond HoxA9 and HoxD3.

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Cathepsin L derived from skeletal muscle cells transfected with bFGF promotes endothelial cell migration

Experimental & Molecular Medicine ◽

10.3858/emm.2011.43.4.022 ◽

2011 ◽

Vol 43 (4) ◽

pp. 179 ◽

Cited By ~ 20

Author(s):

Ji Hyung Chung ◽

Eun Kyoung Im ◽

Taewon Jin ◽

Seung-Min Lee ◽

Soo Hyuk Kim ◽

...

Keyword(s):

Skeletal Muscle ◽

Cell Migration ◽

Endothelial Cell ◽

Cathepsin L ◽

Muscle Cells ◽

Skeletal Muscle Cells ◽

Endothelial Cell Migration

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Oroxylin a Attenuates Limb Ischemia by Promoting Angiogenesis via Modulation of Endothelial Cell Migration

Frontiers in Pharmacology ◽

10.3389/fphar.2021.705617 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lusha Zhang ◽

Lu Chen ◽

Chunxiao Li ◽

Hong Shi ◽

Qianyi Wang ◽

...

Keyword(s):

Skeletal Muscle ◽

Cell Migration ◽

Endothelial Cell ◽

Growth Factor ◽

Signaling Pathway ◽

Muscle Cells ◽

Skeletal Muscle Cells ◽

Endothelial Cell Migration ◽

Oroxylin A ◽

Fibroblast Growth Factor Basic

Oroxylin A (OA) has been shown to simultaneously increase coronary flow and provide a strong anti-inflammatory effect. In this study, we described the angiogenic properties of OA. OA treatment accelerated perfusion recovery, reduced tissue injury, and promoted angiogenesis after hindlimb ischemia (HLI). In addition, OA regulated the secretion of multiple cytokines, including vascular endothelial growth factor A (VEGFA), angiopoietin-2 (ANG-2), fibroblast growth factor-basic (FGF-2), and platelet derived growth factor BB (PDGF-BB). Specifically, those multiple cytokines were involved in cell migration, cell population proliferation, and angiogenesis. These effects were observed at 3, 7, and 14 days after HLI. In skeletal muscle cells, OA promoted the release of VEGFA and ANG-2. After OA treatment, the conditioned medium derived from skeletal muscle cells was found to significantly induce endothelial cell (EC) proliferation. OA also induced EC migration by activating the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil kinase 2 (ROCK-II) signaling pathway and the T-box20 (TBX20)/prokineticin 2 (PROK2) signaling pathway. In addition, OA was able to downregulate the number of macrophages and neutrophils, along with the secretion of interleukin-1β, at 3 days after HLI. These results expanded current knowledge about the beneficial effects of OA in angiogenesis and blood flow recovery. This research could open new directions for the development of novel therapeutic intervention for patients with peripheral artery disease (PAD).

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