Increasing TRPV4 expression restores flow-induced dilation impaired in mesenteric arteries with aging

Du, Juan; Wang, Xia; Li, Jie; Guo, Jizheng; Liu, Limei; Ding, Yan; Yang, Yunyun; Li, Zhongwen; Zhu, Jiaquan; Shen, Bing

doi:10.1038/srep22780

Cited by 25 publications

(24 citation statements)

References 32 publications

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“…; Du et al . ). However, the role of TRPV4 channels in ACh‐induced vasodilatation is less clear (Köhler et al .…”

Section: Mechanisms Underlying Flow‐evoked Ca2+ Signallingmentioning

confidence: 97%

“…These results suggest that both Ca 2+ release from the internal store(s) and store-operated/receptor-operated Ca 2+ -entry through TRPC channels contribute to flow-induced endothelial Ca 2+ signals, and that Ca 2+ entry through TRPC channels is required to refill the internal store(s). TRP vanilloid 4 (TRPV4) channels are reported to contribute to flow-induced vasodilatation (Hartmannsgruber et al 2007;Mendoza et al 2010; Du et al 2016). However, the role of TRPV4 channels in ACh-induced vasodilatation is less clear (Köhler et al 2006;Zhang et al 2009;Sukumaran et al 2013;Pankey et al 2014).…”

Section: Mechanisms Underlying Flow-evoked Ca 2+ Signallingmentioning

confidence: 99%

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Acetylcholine released by endothelial cells facilitates flow‐mediated dilatation

Wilson

Lee

McCarron

2016

The Journal of Physiology

103

124

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Key points The endothelium plays a pivotal role in the vascular response to chemical and mechanical stimuli.The endothelium is exquisitely sensitive to ACh, although the physiological significance of ACh‐induced activation of the endothelium is unknown.In the present study, we investigated the mechanisms of flow‐mediated endothelial calcium signalling.Our data establish that flow‐mediated endothelial calcium responses arise from the autocrine action of non‐neuronal ACh released by the endothelium. AbstractCirculating blood generates frictional forces (shear stress) on the walls of blood vessels. These frictional forces critically regulate vascular function. The endothelium senses these frictional forces and, in response, releases various vasodilators that relax smooth muscle cells in a process termed flow‐mediated dilatation. Although some elements of the signalling mechanisms have been identified, precisely how flow is sensed and transduced to cause the release of relaxing factors is poorly understood. By imaging signalling in large areas of the endothelium of intact arteries, we show that the endothelium responds to flow by releasing ACh. Once liberated, ACh acts to trigger calcium release from the internal store in endothelial cells, nitric oxide production and artery relaxation. Flow‐activated release of ACh from the endothelium is non‐vesicular and occurs via organic cation transporters. ACh is generated following mitochondrial production of acetylCoA. Thus, we show ACh is an autocrine signalling molecule released from endothelial cells, and identify a new role for the classical neurotransmitter in endothelial mechanotransduction.

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“…; Du et al . ). However, the role of TRPV4 channels in ACh‐induced vasodilatation is less clear (Köhler et al .…”

Section: Mechanisms Underlying Flow‐evoked Ca2+ Signallingmentioning

confidence: 97%

Section: Mechanisms Underlying Flow-evoked Ca 2+ Signallingmentioning

confidence: 99%

Acetylcholine released by endothelial cells facilitates flow‐mediated dilatation

Wilson

Lee

McCarron

2016

The Journal of Physiology

103

124

View full text Add to dashboard Cite

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“…AEA and AA use EET acids to activate TRPV4 channels and cause vasorelaxation [69]. Impaired TRPV4-mediated Ca 2+ signalling causes endothelial dysfunction, which prompts TRPV4 to be a potential target for clinical treatment of age-related vascular system diseases and for hypertension treatment [169]. Furthermore, TRPV4 activity is in part regulated by caveolin-1 and this channel requires caveolar location to function properly, which may have clinical significance in the development of pathological states like atherosclerosis associated with hypercholesterolemia [170].…”

Section: Cardiovascular Diseasesmentioning

confidence: 99%

Lipids as central modulators of sensory TRP channels

Ciardo

Ferrer-Montiel

2017

Biochimica et Biophysica Acta (BBA) - Biomembranes

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The transient receptor potential (TRP) ion channel family is involved in a diversity of physiological processes including sensory and homeostatic functions, as well as muscle contraction and vasomotor control. Their dysfunction contributes to the etiology of several diseases, being validated as therapeutic targets. These ion channels may be activated by physical or chemical stimuli and their function is highly influenced by signaling molecules activated by extracellular signals. Notably, as integral membrane proteins, lipid molecules also modulate their membrane location and function either by direct interaction with the channel structure or by modulating the physico-chemical properties of the cellular membrane. This lipid-based modulatory effect is being considered an alternative and promising approach to regulate TRP channel dysfunction in diseases. Here, we review the current progress in this exciting field highlighting a complex channel regulation by a large diversity of lipid molecules and suggesting some diseases that may benefit from a membrane lipid therapy. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

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“…Immunostaining was performed as previously described . Briefly, ASMCs were seeded on glass coverslips and fixed with 2% paraformaldehyde for 30 minutes.…”

Section: Methodsmentioning

confidence: 99%

Inflammatory cytokines tumour necrosis factor‐α and interleukin‐8 enhance airway smooth muscle contraction by increasing L‐type Ca²⁺ channel expression

Ding

Zhang

et al. 2018

Clin Exp Pharma Physio

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Inflammation elevates intracellular calcium concentrations ([Ca ] ) in airway smooth muscle (ASM). The L-type Ca channel (L-VDCC) plays an important role in regulating Ca influx in ASM. However, the role of L-VDCC in the inflammatory cytokine-induced pathology of ASM remains unclear. In the present study, we used calcium imaging and isometric tension measurements to assess the role of L-VDCC in agonist-induced [Ca ] rise and the associated contractions in mouse ASM, and we used immunoblotting to identify L-VDCC protein expression levels in mouse ASM after exposure to tumour necrosis factor alpha (TNF-α) or interleukin-8 (IL-8). Our results showed that high-K - or carbachol-induced contractions of mouse ASM were significantly greater after pretreatment with TNF-α or IL-8 for 24 hours. Both verapamil and nifedipine, L-VDCC inhibitors, abolished this increased contraction induced by TNF-α or IL-8 pretreatment. Moreover, TNF-α treatment enhanced carbachol-induced Ca influx in ASM cells, and this effect was abrogated by verapamil. Additionally, immunoblotting results showed that preincubation of mouse ASM with TNF-α or IL-8 also enhanced L-VDCC protein expression. On the basis of these findings, we concluded that proinflammatory cytokines, such as TNF-α and IL-8, increase the expression level of L-VDCC, which in turn contributes to augmented agonist-induced ASM contractions. This effect of inflammation on L-VDCC expression in ASM may be associated with airway hyper-responsiveness and involved in the development of asthma.

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Increasing TRPV4 expression restores flow-induced dilation impaired in mesenteric arteries with aging

Cited by 25 publications

References 32 publications

Acetylcholine released by endothelial cells facilitates flow‐mediated dilatation

Acetylcholine released by endothelial cells facilitates flow‐mediated dilatation

Lipids as central modulators of sensory TRP channels

Inflammatory cytokines tumour necrosis factor‐α and interleukin‐8 enhance airway smooth muscle contraction by increasing L‐type Ca²⁺ channel expression

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Increasing TRPV4 expression restores flow-induced dilation impaired in mesenteric arteries with aging

Cited by 25 publications

References 32 publications

Acetylcholine released by endothelial cells facilitates flow‐mediated dilatation

Acetylcholine released by endothelial cells facilitates flow‐mediated dilatation

Lipids as central modulators of sensory TRP channels

Inflammatory cytokines tumour necrosis factor‐α and interleukin‐8 enhance airway smooth muscle contraction by increasing L‐type Ca2+ channel expression

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Product

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About

Inflammatory cytokines tumour necrosis factor‐α and interleukin‐8 enhance airway smooth muscle contraction by increasing L‐type Ca²⁺ channel expression