The TNF-α/Sphingosine-1-Phosphate Signaling Axis Drives Myogenic Responsiveness in Heart Failure

Kroetsch, Jeffrey T.; Bolz, Steffen‐Sebastian

doi:10.1159/000350528

Cited by 12 publications

(8 citation statements)

References 65 publications

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“…GPCRs proposed to be involved in myogenic vasoconstriction comprise a heterogeneous group of receptors including purinergic P2Y 6 , thromboxane A 2 (TP), sphingosine-1-phosphate, angiotensin AT 1 and cysteinyl leukotriene 1 (CysLT 1 ) receptors (Mederos y Schnitzler et al, 2008; Schleifenbaum et al, 2014; Storch et al, 2015; Kauffenstein et al, 2016; Kroetsch and Bolz, 2013), which may play different roles in myogenic vasoconstriction depending on the vascular bed and the physiological context. We have not analyzed which receptor is involved in myogenic vasoconstriction in mesenteric and cerebral arteries.…”

Section: Discussionmentioning

confidence: 99%

“…More recently, several GPCRs have been involved in the myogenic response of vascular smooth muscle cells (Kauffenstein et al, 2012; Mederos Y Schnitzler et al, 2016). These include the purinergic P2Y 6 receptor, the thromboxane A 2 (TP) receptor, sphingosine-1-phosphate receptors as well as the angiotensin AT 1 receptor and the cysteinyl leukotriene one receptors (CysLT 1 Rs) (Mederos y Schnitzler et al, 2008; Schleifenbaum et al, 2014; Storch et al, 2015; Kauffenstein et al, 2016; Kroetsch and Bolz, 2013). While stretch-induced activation of P2Y 6 , TP and S1P receptors is believed to involve the release of agonistic ligands (Kauffenstein et al, 2012; Kauffenstein et al, 2016; Kroetsch and Bolz, 2013), evidence has been provided that mechanical activation of AT 1 and CysLT 1 receptors occurs in an agonist-independent manner (Mederos Y Schnitzler et al, 2016; Mederos y Schnitzler et al, 2008; Storch et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Myogenic vasoconstriction requires G12/G13 and LARG to maintain local and systemic vascular resistance

Chennupati

Wirth

Favre

et al. 2019

eLife

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Myogenic vasoconstriction is an autoregulatory function of small arteries. Recently, G-protein-coupled receptors have been involved in myogenic vasoconstriction, but the downstream signalling mechanisms and the in-vivo-function of this myogenic autoregulation are poorly understood. Here, we show that small arteries from mice with smooth muscle-specific loss of G12/G13 or the Rho guanine nucleotide exchange factor ARHGEF12 have lost myogenic vasoconstriction. This defect was accompanied by loss of RhoA activation, while vessels showed normal increases in intracellular [Ca2+]. In the absence of myogenic vasoconstriction, perfusion of peripheral organs was increased, systemic vascular resistance was reduced and cardiac output and left ventricular mass were increased. In addition, animals with defective myogenic vasoconstriction showed aggravated hypotension in response to endotoxin. We conclude that G12/G13- and Rho-mediated signaling plays a key role in myogenic vasoconstriction and that myogenic tone is required to maintain local and systemic vascular resistance under physiological and pathological condition.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Myogenic vasoconstriction requires G12/G13 and LARG to maintain local and systemic vascular resistance

Chennupati

Wirth

Favre

et al. 2019

eLife

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“…Another study demonstrated a clear involvement of the P2Y purinergic receptor in the development of mesenteric myogenic tone with implicated signaling to RhoA ( Kauffenstein et al, 2016 ). Interestingly, activation of sphingosine-1-phosphate (S1P) receptors in response to pressure-induced S1P generation could be another mechanism by which a GPCR contribute to mechanotransduction ( Kroetsch and Bolz, 2013 ; Sauve et al, 2016 ). This pathway was linked early on to the activation of RhoA/ROK signaling ( Bolz et al, 2003 ).…”

Section: The Molecular Mechanism Of the Myogenic Responsementioning

confidence: 99%

ROK and Arteriolar Myogenic Tone Generation: Molecular Evidence in Health and Disease

El-Yazbi

Abd-Elrahman

2017

Front. Pharmacol.

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The myogenic response is an inherent property of resistance arteries that warrants a relatively constant blood flow in response to changes in perfusion pressure and protect delicate organs from vascular insufficiencies and excessive blood flow. This fundamental phenomenon has been extensively studied aiming to elucidate the underlying mechanisms triggering smooth muscle contraction in response to intraluminal pressure elevation, particularly, Rho-associated kinase (ROK)-mediated Ca2+-independent mechanisms. The size of the resistance arteries limits the capacity to examine changes in protein phosphorylation/expression levels associated with ROK signaling. A highly sensitive biochemical detection approach was beneficial in examining the role of ROK in different force generation mechanisms along the course of myogenic constriction. In this mini review, we summarize recent results showing direct evidence for the contribution of ROK in development of myogenic response at the level of mechanotransduction, myosin light chain phosphatase inhibition and dynamic actin cytoskeleton reorganization. We will also present evidence that alterations in ROK signaling could underlie the progressive loss in myogenic response in a rat model of type 2 diabetes.

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“…Intrinsic vascular smooth muscle cell signaling in the cascade of events leading to augmented total peripheral resistance in HF and the active myogenic response regulates the local increase in microvascular resistance. DUSP5 also contributes to the impaired myogenic response which is an intrinsic property of vascular smooth muscle cell that enhances by the inflammatory cytokine at any given level of transmural pressure [18].…”

Section: Discussionmentioning

confidence: 99%

NADPH Oxidase Inhibition in Heart Failure Improved Vascular Function Associated with Changes in the Novel Genes Expression Revealed by Transcriptome Analysis

Wada¹,

Matsumoto²,

Takayama³

et al. 2017

Cardiovasc Pharm Open Access

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Vascular endothelium-dependent vasorelaxation is diminished and reduced skeletal muscle blood flow and correlates with the severity of symptoms in heart failure (HF) as a result of the significant elevation of superoxide anion (O 2 -) production. There are several sources of (O 2 -) production within vessels, but NADPH oxidase is present in vascular smooth muscle cells and endothelial cells. Therefore oxidative stress may attenuate endothelial function and inhibition of this action may become one of the strategies to treat HF. We previously investigated the global transcriptome analysis in tachycardia induced HF dogs and we selected four core genes, SOCS3, GADD45A, CDKN1A, and DUSP5 which were associated with the p53 pathway-related genes and the inflammatory interleukinrelated genes enhanced expression in HF. We examined therapeutic effects of apocynin (0.3 mg/kg/day) which suppressed generation of (O 2 -) on vascular endothelial function and those gene expressions in the femoral artery. Apocynin significantly increased % femoral blood flow responses by acetylcholine (HF 196.4 ± 24.7% vs. apocynin 342.2 ± 35.4%, P<0.05), suppressed O 2 production (HF 17.9 ± 1.9 LU/mg/min vs. apocynin 12.89 ± 1.6 RLU/mg/ min, P<0.05) and NADPH oxidase activity (HF 124.9 ± 20.4 RLU/mg/min vs. apocynin 63.9 ± 14.7 RLU/mg/min P<0.05) in HF. The agent decreased the levels of SOCS3, GADD45A, CDKN1A and DUSP5 mRNAs expressions. Suppression of oxidative stress improved endothelial dysfunction in HF through pathways closely linked with cell cycles, proliferation, apoptosis and inflammation. We can conclude that the specific inhibition of NADPH oxidase will become one of the promising therapeutic targets in the treatment of HF mediating through novel vascular molecular mechanisms.

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The TNF-α/Sphingosine-1-Phosphate Signaling Axis Drives Myogenic Responsiveness in Heart Failure

Cited by 12 publications

References 65 publications

Myogenic vasoconstriction requires G12/G13 and LARG to maintain local and systemic vascular resistance

Myogenic vasoconstriction requires G12/G13 and LARG to maintain local and systemic vascular resistance

ROK and Arteriolar Myogenic Tone Generation: Molecular Evidence in Health and Disease

NADPH Oxidase Inhibition in Heart Failure Improved Vascular Function Associated with Changes in the Novel Genes Expression Revealed by Transcriptome Analysis

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