Angiotensin II induces focal adhesion kinase/paxillin phosphorylation and cell migration in human umbilical vein endothelial cells

Montiel, Mercedes; Esther, Blanca; Jiménez, Eugenio

doi:10.1016/j.bbrc.2004.12.110

Cited by 38 publications

(28 citation statements)

References 46 publications

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“…We have previously demonstrated that cAMP-GEF can activate PI3K and that the cytoprotective effect of cAMP-GEF in bile acid induced apoptosis is PI3K dependent (25). FAK signaling can be either upstream or downstream of PI3K (13,14,43,44). In our experiments, cAMP-GEF mediated FAK phosphorylation is PI3K dependent placing FAK downstream of PI3K.…”

Section: Discussionsupporting

confidence: 64%

Activation of focal adhesion kinase and JNK contributes to the extracellular matrix and cAMP-GEF mediated survival from bile acid induced apoptosis in rat hepatocytes

Usechak

Gates

Webster

2008

Journal of Hepatology

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Section: Discussionsupporting

confidence: 64%

Activation of focal adhesion kinase and JNK contributes to the extracellular matrix and cAMP-GEF mediated survival from bile acid induced apoptosis in rat hepatocytes

Usechak

Gates

Webster

2008

Journal of Hepatology

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“…PI 3-K is an important mediator of signal transduction from a variety of cell surface receptors including VEGF receptor 2 (Gille et al, 2000), and one well-known function of PI 3-K is regulation of cell migration. Endothelial cell chemotaxis is dependent upon PI 3-K activation of intracellular signaling cascades (Arefieva et al, 2005) and inhibition of PI 3-K decreases HUVEC migration (Montiel et al, 2005). Similarly, PI 3-K inhibition with LY294002 blocks FGF-2-stimulated corneal endothelial cell migration into scratch wounds in vitro (Lee and Kay, 2003), and abrogates the increased CEC migration induced by Beta(3)-adrenergic receptor or NGF stimulation (Steinle and Granger, 2003;Steinle et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Heterotypic RPE-choroidal endothelial cell contact increases choroidal endothelial cell transmigration via PI 3-kinase and Rac1

Peterson

Wittchen

Geisen³

et al. 2007

Experimental Eye Research

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Age-related macular degeneration (AMD) is the major cause of non-preventable blindness. Severe forms of AMD involve breaching of the retinal pigment epithelial (RPE) barrier by underlying choroidal endothelial cells (CECs), followed by migration into, and subsequent neovascularization of the neurosensory retina. However, little is known about the interactions between RPE and CECs and the signaling events leading to CEC transmigration. While soluble chemotactic factors secreted from RPE can contribute to inappropriate CEC transmigration, other unidentified stimuli may play an additional role. Using a coculture model that maintains the natural structural orientation of CECs to the basal aspect of RPE, we show that "contact" with RPE and/or RPE extracellular matrix increases CEC transmigration of the RPE barrier. From a biochemical standpoint, contact between CECs and RPE results in an increase in the activity of the GTPase Rac1 within the CECs; this increase is dependent on upstream activation of PI 3-K and Akt1. To confirm a link between these signaling molecules and increased CEC transmigration, we performed transmigration assays while inhibiting both PI 3-K and Rac1 activity, and observed that both decreased CEC transmigration. We hypothesize that contact between CECs and RPE stimulates a signaling pathway involving PI 3-K, Akt1, and Rac1 that facilitates CEC transmigration across the RPE barrier, an important step in the development of neovascular AMD.

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“…EGFR transactivation has been studied principally in smooth muscle cells, but several reports have indicated that EGFR activation is also important in endothelial cells. 35,36 The use of murine models with endothelium-or smooth muscle-specific deletions of the EGFR gene should provide further insight into this issue.…”

Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor Receptor Mediates the Vascular Dysfunction But Not the Remodeling Induced by Aldosterone/Salt

et al. 2011

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Abstract-Pathophysiological aldosterone (aldo)/mineralocorticoid receptor signaling has a major impact on the cardiovascular system, resulting in hypertension and vascular remodeling. Mineralocorticoids induce endothelial dysfunction, decreasing vasorelaxation in response to acetylcholine and increasing the response to vasoconstrictors. Activation of the epidermal growth factor receptor (EGFR) is thought to mediate the vascular effects of aldo, but this has yet to be demonstrated in vivo. In this study, we analyzed the molecular and functional vascular consequences of aldo-salt challenge in the waved 2 mouse, a genetic model with a partial loss of EGFR tyrosine kinase activity. Deficient EGFR activity is associated with global oxidative stress and endothelial dysfunction. A decrease in EGFR activity did not affect the arterial wall remodeling process induced by aldo-salt. By contrast, normal EGFR activity was required for the aldo-induced enhancement of phenylephrine-and angiotensin II-mediated vasoconstriction. In conclusion, this in vivo study demonstrates that EGFR plays a key role in aldosterone-mediated vascular reactivity. Clinical trials (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study and Randomized Aldactone Evaluation Study) have demonstrated the beneficial effects of administering low doses of pharmacological antagonists of the mineralocorticoid receptor (MR; the receptor of the mineralocorticoid hormone aldosterone [aldo]) to patients with heart failure, with improvements in survival rate and morbidity. 1,2 These clinical benefits may partly result from improved vascular function. 3 The MR is expressed in both endothelium and smooth muscle, 4 and the vessels are now considered to be direct targets of aldo. 5 In the mouse, the 11␤-hydroxysteroid dehydrogenase type II enzyme is expressed in the endothelium but not in the smooth muscle, 4,6 at variance with humans. 7 Therefore, in the mouse, aldo is the specific ligand of the MR in the endothelium but not in the smooth muscle, where glucocorticoids could also activate MR. MR activation affects endothelial function and vascular tone: aldo infusion induces endothelial dysfunction, decreasing vasorelaxation in response to acetylcholine (Ach), and increasing the response to various vasoconstrictors. 5,8,9 We showed recently that an increase in MR signaling in the endothelium is associated with an increase in blood pressure and altered vascular tone. 4 Moreover, patients with primary aldosteronism have a higher aortic wall thickness than those with primary hypertension. 10 Aldo is, thus, recognized as a cardiovascular risk factor that exacerbates vascular injury, 3 although the underlying mechanisms remain unclear.It has been suggested that the epidermal growth factor receptor (EGFR) could play a key role in the cardiovascular effects of aldo. 11 In cultured cells, downstream EGFR signaling cascades are induced by aldo or prevented by MR blockade on aldo stimulation. 12 Increases in EGFR expression and/or activation have...

show abstract

Angiotensin II induces focal adhesion kinase/paxillin phosphorylation and cell migration in human umbilical vein endothelial cells

Cited by 38 publications

References 46 publications

Activation of focal adhesion kinase and JNK contributes to the extracellular matrix and cAMP-GEF mediated survival from bile acid induced apoptosis in rat hepatocytes

Activation of focal adhesion kinase and JNK contributes to the extracellular matrix and cAMP-GEF mediated survival from bile acid induced apoptosis in rat hepatocytes

Heterotypic RPE-choroidal endothelial cell contact increases choroidal endothelial cell transmigration via PI 3-kinase and Rac1

Epidermal Growth Factor Receptor Mediates the Vascular Dysfunction But Not the Remodeling Induced by Aldosterone/Salt

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