Arteriogenesis: A focus on signal transduction cascades and transcription factors

Deindl, Elisabeth

doi:10.1160/th07-04-0261

Cited by 23 publications

(19 citation statements)

References 57 publications

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“…Abra initiates SRF-dependent transcription. Apart from previous findings of SRF-dependent transcription during arteriogenesis (reviewed in 28 ), we were able to demonstrate that SRF itself is upregulated under conditions of high FSS. RhoA-dependent regulation of the actin cytoskeleton selectively regulates SMC differentiation marker gene expression by modulating SRF dependent transcription.…”

Section: Troidl Et Almentioning

confidence: 43%

Actin-Binding Rho Activating Protein ( Abra ) Is Essential for Fluid Shear Stress-Induced Arteriogenesis

Troidl

Rüding

Cai

et al. 2009

ATVB

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Objective— Arteriogenesis, the development of a collateral circulation, is important for tissue survival but remains functionally defective because of early normalization of fluid shear stress (FSS). Using a surgical model of chronically elevated FSS we showed that rabbits exhibited normal blood flow reserve after femoral artery ligature (FAL). Inhibition of the Rho pathway by Fasudil completely blocked the beneficial effect of FSS. In a genome-wide gene profiling we identified actin-binding Rho activating protein ( Abra ), which was highly upregulated in growing collaterals. Methods and Results— qRT-PCR and Western blot confirmed highly increased FSS-dependent expression of Abra in growing collaterals. NO blockage by L-NAME abolished FSS-generated Abra expression as well as the whole arteriogenic process. Cell culture studies demonstrated an Abra-triggered proliferation of smooth muscle cells through a mechanism that requires Rho signaling. Local intracollateral adenoviral overexpression of Abra improved collateral conductance by 60% in rabbits compared to the natural response after FAL. In contrast, targeted deletion of Abra in CL57BL/6 mice led to impaired arteriogenesis. Conclusions— FSS-induced Abra expression during arteriogenesis is triggered by NO and leads to stimulation of collateral growth by smooth muscle cell proliferation.

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Section: Troidl Et Almentioning

confidence: 43%

Actin-Binding Rho Activating Protein ( Abra ) Is Essential for Fluid Shear Stress-Induced Arteriogenesis

Troidl

Rüding

Cai

et al. 2009

ATVB

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“…9 SRF as well as MRTFs are recognized as liaisons connecting the key pathways of arteriogenesis, ie, Rho pathway with downstream genes. 47 Therefore, we speculate that FHL-2 in vascular SMCs might contribute the process of atherosclerosis or angiogenesis through suppressing phenotypic switching.…”

Section: Discussionmentioning

confidence: 89%

FHL-2 Suppresses VEGF-Induced Phosphatidylinositol 3-Kinase/Akt Activation via Interaction With Sphingosine Kinase-1

Hayashi

Nakagami

Takami

et al. 2009

ATVB

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Objective-In the functional screening of a human heart cDNA library to identify a novel antiangiogenic factor, the prime candidate gene was "four-and-a-half LIM only protein-2" (FHL-2). The goal of this study is to clear the mechanism of antiangiogenic signaling of FHL-2 in endothelial cells (ECs). Methods and Results-Overexpressed FHL-2 strongly inhibited vascular endothelial growth factor (VEGF)-induced EC migration. In the angiogenic signaling, we focused on sphingosine kinase-1 (SK1), which produces sphingosine-1-phosphate (S1P), a bioactive sphingolipid, as a potent angiogenic mediator in ECs. Immunoprecipitation and immunostaining analysis showed that FHL-2 might bind to SK1. Importantly, overexpression of FHL-2 in ECs inhibited VEGF-induced SK1 activity, phosphatidylinositol 3-kinase activity, and phosphorylation of Akt and eNOS. In contrast, overexpression of FHL-2 had no effect on S1P-induced Akt phosphorylation. Interestingly, VEGF stimulation decreased the binding of FHL-2 and SK1. Depletion of FHL-2 by siRNA increased EC migration accompanied with SK1 and Akt activation, and increased the expression of VEGF receptor-2 which further enhanced VEGF signaling. Furthermore, injection of FHL-2 mRNA into Xenopus embryos resulted in inhibition of vascular network development, assessed by in situ hybridization with endothelial markers. Conclusions-FHL-

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“…The observed phenotype is similar to the effect of vegf knockdown and is not rescued by VEGF injections (39). Further evidence of a potential role for this pathway in arterial specification comes from observation of increased P-ERK expression in newly forming arterial vessels (8,41) and from a study of gridlock mutants (14). However, to our knowledge, no study to date has shown that ERK activation can promote arterial morphogenesis and branching during development and in adult tissues.…”

Section: Discussionmentioning

confidence: 69%

ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish

Ren¹,

Deng²,

et al. 2010

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Arterial morphogenesis is an important and poorly understood process. In particular, the signaling events controlling arterial formation have not been established. We evaluated whether alterations in the balance between ERK1/2 and PI3K signaling pathways could stimulate arterial formation in the setting of defective arterial morphogenesis in mice and zebrafish. Increased ERK1/2 activity in mouse ECs with reduced VEGF responsiveness was achieved in vitro and in vivo by downregulating PI3K activity, suppressing Akt1 but not Akt2 expression, or introducing a constitutively active ERK1/2 construct. Such restoration of ERK1/2 activation was sufficient to restore impaired arterial development and branching morphogenesis in synectin-deficient mice and synectin-knockdown zebrafish. The same approach effectively stimulated arterial growth in adult mice, restoring arteriogenesis in mice lacking synectin and in atherosclerotic mice lacking both LDL-R and ApoB48. We therefore conclude that PI3K-ERK1/2 crosstalk plays a key role in the regulation of arterial growth and that the augmentation of ERK signaling via suppression of the PI3K signaling pathway can effectively stimulate arteriogenesis.

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Arteriogenesis: A focus on signal transduction cascades and transcription factors

Cited by 23 publications

References 57 publications

Actin-Binding Rho Activating Protein ( Abra ) Is Essential for Fluid Shear Stress-Induced Arteriogenesis

Actin-Binding Rho Activating Protein ( Abra ) Is Essential for Fluid Shear Stress-Induced Arteriogenesis

FHL-2 Suppresses VEGF-Induced Phosphatidylinositol 3-Kinase/Akt Activation via Interaction With Sphingosine Kinase-1

ERK1/2-Akt1 crosstalk regulates arteriogenesis in mice and zebrafish

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