Targeting γ-secretases protect against angiotensin II-induced cardiac hypertrophy

Rivera‐Torres, José; Guzmán‐Martínez, Gabriela; Villa‐Bellosta, Ricardo; Orbe, Josune; González‐Gómez, Cristina; Serrano, Manuel; Dı́ez, Javier; Andrés, Vicente; Maraver, Antonio

doi:10.1097/hjh.0000000000000463

Cited by 10 publications

(8 citation statements)

References 21 publications

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“…However, the phenotype could involve developmental and/or constitutive suppression of Notch3. In inducible ␥-secretase complex silencing mice, ANG IIinduced blood pressure elevation and left ventricular hypertrophy are both attenuated (871). In addition, it is well recognized that NICD partners with the transcriptional activator Mastermind and a DNA-binding protein, CBF1/Su(H)/Lag2 protein (CSL), targeting the complex to gene promoters containing the consensus motif GTGGGAA, for transcriptional activation.…”

Section: Notch Pathwaymentioning

confidence: 99%

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

812

780

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The renin-angiotensin-aldosterone system plays crucial roles in cardiovascular physiology and pathophysiology. However, many of the signaling mechanisms have been unclear. The angiotensin II (ANG II) type 1 receptor (ATR) is believed to mediate most functions of ANG II in the system. ATR utilizes various signal transduction cascades causing hypertension, cardiovascular remodeling, and end organ damage. Moreover, functional cross-talk between ATR signaling pathways and other signaling pathways have been recognized. Accumulating evidence reveals the complexity of ANG II signal transduction in pathophysiology of the vasculature, heart, kidney, and brain, as well as several pathophysiological features, including inflammation, metabolic dysfunction, and aging. In this review, we provide a comprehensive update of the ANG II receptor signaling events and their functional significances for potential translation into therapeutic strategies. ATR remains central to the system in mediating physiological and pathophysiological functions of ANG II, and participation of specific signaling pathways becomes much clearer. There are still certain limitations and many controversies, and several noteworthy new concepts require further support. However, it is expected that rigorous translational research of the ANG II signaling pathways including those in large animals and humans will contribute to establishing effective new therapies against various diseases.

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Section: Notch Pathwaymentioning

confidence: 99%

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

812

780

View full text Add to dashboard Cite

show abstract

“…AT1 receptor stimulates Notch signaling pathway through an increase of γ-secretase enzymatic activity, mediating VSMCs proliferation and migration (143). Notch inhibition or γ-secretase complex silencing in mice attenuates hypertension induced by AngII (144, 145). Notch3 −/− mice show attenuated renal vascular constriction, vessel wall thickening and hypertension induced by AngII.…”

Section: Cascades Of Wnt Notch Hippo and Mitochondriamentioning

confidence: 99%

AT1 receptor signaling pathways in the cardiovascular system

Kawai

Forrester

O’Brien

et al. 2017

Pharmacological Research

182

126

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The importance of the renin angiotensin aldosterone system in cardiovascular physiology and pathophysiology has been well described whereas the detailed molecular mechanisms remain elusive. The angiotensin II type 1 receptor (AT1 receptor) is one of the key players in the renin angiotensin aldosterone system. The AT1 receptor promotes various intracellular signaling pathways resulting in hypertension, endothelial dysfunction, vascular remodeling and end organ damage. Accumulating evidence shows the complex picture of AT1 receptor-mediated signaling; AT1 receptor-mediated heterotrimeric G protein-dependent signaling, transactivation of growth factor receptors, NADPH oxidase and ROS signaling, G protein-independent signaling, including the β-arrestin signals and interaction with several AT1 receptor interacting proteins. In addition, there is functional cross-talk between the AT1 receptor signaling pathway and other signaling pathways. In this review, we will summarize an up to date overview of essential AT1 receptor signaling events and their functional significances in the cardiovascular system.

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“…To test whether Notch pathway activity is necessary for the growth of EGFR-driven tumors, we treated EGFR T790M/L858R mice with doxycycline for 8 weeks to induce tumor formation, and then randomly assigned them to 3 groups: (i) control group, treated with vehicle and IgG antibody control; (ii) GSI group, treated with dibenzazepine (DBZ), a potent and selective GSI; and (iii) anti-NRR1/NRR3 group, treated with blocking antibodies against NOTCH1 and NOTCH3, according to previously described treatment regimens (25)(26)(27). After 5 weeks of treatment, tumors represented more than 40% of the lung area in the control group, but only 20% and 10% in the DBZ and anti-NRR1/NRR3 groups, respectively ( Figure 1C).…”

Section: Introductionmentioning

confidence: 99%

Notch inhibition overcomes resistance to tyrosine kinase inhibitors in EGFR-driven lung adenocarcinoma

Mur¹,

Bernardo²,

Papon³

et al. 2019

Journal of Clinical Investigation

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Targeting γ-secretases protect against angiotensin II-induced cardiac hypertrophy

Cited by 10 publications

References 21 publications

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

AT1 receptor signaling pathways in the cardiovascular system

Notch inhibition overcomes resistance to tyrosine kinase inhibitors in EGFR-driven lung adenocarcinoma

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