A gain-of-function SNP in TRPC4 cation channel protects against myocardial infarction

Jung, Carole; Gené, Gemma G.; Tomàs, Marta; Plata, Cristina; Selent, Jana; Pastor, Manuel; Fandos, César; Sentı́, Mariano; Lucas, Gavin; Elosúa, Roberto; Valverde, Miguel A.

doi:10.1093/cvr/cvr083

Cited by 30 publications

(25 citation statements)

References 39 publications

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“…5 On the basis of recent genome-wide association studies, calcium channels are implicated in the pathophysiology of BD, 18,19 and these channels also appear to be salient to CVD. 20,21 MDD and BD are the first and fourth most disabling conditions, respectively, among adolescents worldwide. 22 BD involves repeated episodes of mania/hypomania (elated or irritable mood together with other symptoms) that generally, but not always, alternate with episodes of depression (sadness or lack of interest/pleasure along with other symptoms).…”

Section: Circulationmentioning

confidence: 99%

Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease

Goldstein¹,

Carnethon²,

Matthews³

et al. 2015

Circulation

404

290

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Abstract-In the 2011 "Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children andAdolescents," several medical conditions among youth were identified that predispose to accelerated atherosclerosis and early cardiovascular disease (CVD), and risk stratification and management strategies for youth with these conditions were elaborated. Major depressive disorder (MDD) and bipolar disorder (BD) among youth satisfy the criteria set for, and therefore merit inclusion among, Expert Panel tier II moderate-risk conditions. The combined prevalence of MDD and BD among adolescents in the United States is ≈10%, at least 10 times greater than the prevalence of the existing moderate-risk conditions combined. The high prevalence of MDD and BD underscores the importance of positioning these diseases alongside other pediatric diseases previously identified as moderate risk for CVD. The overall objective of this statement is to increase awareness and recognition of MDD and BD among youth as moderate-risk conditions for early CVD. To achieve this objective, the primary specific aims of this statement are to (1) summarize evidence that MDD and BD are tier II moderate-risk conditions associated with accelerated atherosclerosis and early CVD and (2)

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Section: Circulationmentioning

confidence: 99%

Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease

Goldstein¹,

Carnethon²,

Matthews³

et al. 2015

Circulation

404

290

View full text Add to dashboard Cite

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“…Whether TRPC4 contributes to the repetitive Ca 2+ spikes arising in HUVECs both before (spontaneous) and after (histamine-evoked) tubule formation in a store-dependent or independent manner has yet to be elucidated [224] . A single nucleotide polymorphism in the TRPC4 gene has been associated with protection from myocardial infarction and results in a larger current density when the mis-sense channel is expressed in heterologous cell systems [266] . This feature is likely due to a less bulky Val-957, which favors TRPC4 insertion into the plasma membrane and its interaction with the catalytic site of the tyrosine kinase that phosphorylates the channel at Tyr-959 [266] .…”

Section: +(Rt-pcr)mentioning

confidence: 99%

“…A single nucleotide polymorphism in the TRPC4 gene has been associated with protection from myocardial infarction and results in a larger current density when the mis-sense channel is expressed in heterologous cell systems [266] . This feature is likely due to a less bulky Val-957, which favors TRPC4 insertion into the plasma membrane and its interaction with the catalytic site of the tyrosine kinase that phosphorylates the channel at Tyr-959 [266] . Less information is available on the role played by TRPC5 in ECs, where it may be constitutively open and also participate to ATP-induced Ca 2+ entry [267] .…”

Section: +(Rt-pcr)mentioning

confidence: 99%

Update on vascular endothelial Ca²⁺signalling: A tale of ion channels, pumps and transporters

Moccia

Berra‐Romani²,

Tanzi³

2012

WJBC

110

192

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A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that mediates a plethora of cardiovascular processes. The activation of ECs from as state of quiescence is, therefore, regarded among the early events leading to the onset and progression of potentially lethal diseases, such as hypertension, myocardial infarction, brain stroke, and tumor. Intracellular Ca 2+ signals have long been know to play a central role in the complex network of signaling pathways regulating the endothelial functions. Notably, recent work has outlined how any change in the pattern of expression of endothelial channels, transporters and pumps involved in the modulation of intracellular Ca 2+ levels may dramatically affect whole body homeostasis. Vascular ECs may react to both mechanical and chemical stimuli by generating a variety of intracellular Ca 2+ signals, ranging from brief, localized Ca 2+ pulses to prolonged Ca 2+ oscillations engulfing the whole cytoplasm. The well-defined spatiotemporal profile of the subcellular Ca 2+ signals elicited in ECs by specific extracellular inputs depends on the interaction between Ca 2+ releasing channels, which are located both on the plasma membrane and in a number of intracellular organelles, and Ca 2+ removing systems. The present article aims to summarize both the past and recent literature in the field to provide a clear-cut picture of our current knowledge on the molecular nature and the role played by the components of the Ca 2+ machinery in vascular ECs under both physiological and pathological conditions.

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“…This mechanism underlying protection is an improved endothelial function, but this needs more investigation. 29 In other study, photoparoxysmal responses (PPR) characterized by abnormal visual sensitivity of the brain to photic stimulation which is generally related to idiopathic generalized epilepsies (IGE) are related to various SNPs in the TRPC4 gene. 30 This relation was not significant after corresponding corrections, this trend toward relation of TRPC4 variants and PPR/IGE is of especial interest and deserves further investigation since it could be shown that TRPC4 is involved in numerous functions related with epilepsy.…”

Section: Trpc4 Channelsmentioning

confidence: 99%

The Roles of Rasd1 small G proteins and leptin in the activation of TRPC4 transient receptor potential channels

et al. 2015

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#These authors contributed equally to this work TRPC4 is important regulators of electrical excitability in gastrointestinal myocytes, pancreatic b-cells and neurons. Much is known regarding the assembly and function of these channels including TRPC1 as a homotetramer or a heteromultimer and the roles that their interacting proteins play in controlling these events. Further, they are one of the best-studied targets of G protein-coupled receptors and growth factors in general and Ga i/o and Ga q protein coupled receptor or epidermal growth factor and leptin in particular. However, our understanding of the roles of small G proteins and leptin on TRPC4 channels is still rudimentary. We discuss potential roles for Rasd1 small G protein and leptin in channel activation in addition to their known role in cellular signaling.

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A gain-of-function SNP in TRPC4 cation channel protects against myocardial infarction

Cited by 30 publications

References 39 publications

Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease

Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease

Update on vascular endothelial Ca²⁺signalling: A tale of ion channels, pumps and transporters

The Roles of Rasd1 small G proteins and leptin in the activation of TRPC4 transient receptor potential channels

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A gain-of-function SNP in TRPC4 cation channel protects against myocardial infarction

Cited by 30 publications

References 39 publications

Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease

Major Depressive Disorder and Bipolar Disorder Predispose Youth to Accelerated Atherosclerosis and Early Cardiovascular Disease

Update on vascular endothelial Ca2+signalling: A tale of ion channels, pumps and transporters

The Roles of Rasd1 small G proteins and leptin in the activation of TRPC4 transient receptor potential channels

Contact Info

Product

Resources

About

Update on vascular endothelial Ca²⁺signalling: A tale of ion channels, pumps and transporters