Serotonin contribution to cardiac valve degeneration: new insights for novel therapies?

Ayme-Dietrich, Estelle; Lawson, Roland; Da-Silva, Sylvia; Mazzucotelli, J. P.; Monassier, Laurent

doi:10.1016/j.phrs.2018.09.009

Cited by 24 publications

(39 citation statements)

References 76 publications

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“…The remodeling of cardiac valve interstitial cells, a heterogeneous population of cells responsible for maintaining the structural integrity and normal functioning of the valve, is key to understanding mitral and aortic valve dysfunctions in pulmonary hypertension. The role of 5-HT 2B receptor activation by 5-HT in this pathology caused by fenfluramine treatment is well known, but serotonylation of filamin-A has also been implicated 26 ( Figure 2 ). Pancreatic β-cells capture extracellular 5-HT via SERT.…”

Section: Receptor-independent 5-ht Signaling: Serotonylationmentioning

confidence: 99%

Novel and atypical pathways for serotonin signaling

Bockaert¹,

Bécamel²,

Chaumont‐Dubel³

et al. 2021

Fac Rev

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Serotonin (5-HT) appeared billions of years before 5-HT receptors and synapses. It is thus not surprising that 5-HT can control biological processes independently of its receptors. One example is serotonylation, which consists of covalent binding of 5-HT to the primary amine of glutamine. Over the past 20 years, serotonylation has been involved in the regulation of many signaling mechanisms. One of the most striking examples is the recent evidence that serotonylation of histone H3 constitutes an epigenetic mark. However, the pathophysiological role of histone H3 serotonylation remains to be discovered. All but one of the 5-HT receptors are G-protein-coupled receptors (GPCRs). The signaling pathways they control are finely tuned, and new, unexpected regulatory mechanisms are being uncovered continuously. Some 5-HT receptors (5-HT 2C , 5-HT 4 , 5-HT 6 , and 5-HT 7 ) signal through mechanisms that require neither G-proteins nor β-arrestins, the two classical and almost universal GPCR signal transducers. 5-HT 6 receptors are constitutively activated via their association with intracellular GPCR-interacting proteins (GIPs), including neurofibromin 1, cyclin-dependent kinase 5 (Cdk5), and G-protein-regulated inducer of neurite outgrowth 1 (GPRIN1). Interactions of 5-HT 6 receptor with Cdk5 and GPRIN1 are not concomitant but occur sequentially and play a key role in dendritic tree morphogenesis. Furthermore, 5-HT 6 receptor-mediated G-protein signaling in neurons is different in the cell body and primary cilium, where it is modulated by smoothened receptor activation. Finally, 5-HT 2A receptors form heteromers with mGlu 2 metabotropic glutamate receptors. This heteromerization results in a specific phosphorylation of mGlu 2 receptor on a serine residue (Ser 843 ) upon agonist stimulation of 5-HT 2A or mGlu 2 receptor. mGlu 2 receptor phosphorylation on Ser 843 is an essential step in engagement of G i/o signaling not only upon mGlu 2 receptor activation but also following 5-HT 2A receptor activation, and thus represents a key molecular event underlying functional crosstalk between both receptors.

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Section: Receptor-independent 5-ht Signaling: Serotonylationmentioning

confidence: 99%

Novel and atypical pathways for serotonin signaling

Bockaert¹,

Bécamel²,

Chaumont‐Dubel³

et al. 2021

Fac Rev

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“…5-HT2A is additionally located on platelets and involved in activation and aggregation, and it can also be found on cardiomyocytes and fibroblasts. 5-HT4, expressed in cardiac atria and ventricle conducts positive inotropic and lusitropic effects but may also trigger arrhythmias (reviewed in [ 5 ]).…”

Section: Serotoninmentioning

confidence: 99%

Serotonin: a platelet hormone modulating cardiovascular disease

Rieder

Gauchel

Bode

et al. 2020

J Thromb Thrombolysis

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Cardiovascular diseases and depression are significant health burdens and increasing evidence suggests a causal relationship between them. The incidence of depression among patients suffering from cardiovascular disease is markedly elevated, and depression itself is an established cardiovascular risk factor. Serotonin 5-hydroxytryptamin (5-HT), a biogenic amine acting as a neurotransmitter and a peripheral hormone, is involved in the pathogenesis of both, cardiovascular disease and depression. Novel cardiovascular functions of 5-HT have recently been described and will be summarized in this review. 5-HT has a broad spectrum of functions in the cardiovascular system, yet the clinical or experimental data are partly conflicting. There is further research needed to characterize the clinical effects of 5-HT in particular tissues to enable targeted pharmacological therapies.

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“…The identification of endothelial progenitors sharing this receptor in human mitral valve prolapse tissues reveals the relevance of this mechanism in human heart valve remodelling [43]. Many other proposed molecular mechanisms for heart valve degeneration are also probabaly implicated and involve (i) a 5-HT-mediated activation of G-protein receptor signal transduction that results in a local mitogenic effect; (ii) the 5-HT-induced TGF-β1 expression regulates the remodeling of the extracellular matrix via endothelial to mesenchymal transition; (iii) finally, serotonylation and intracellular interaction with cytoskeletal components, such as Rac1 [44], Rab4 [45] and Filamin-A [46].…”

Section: Cardiovascular Functions Of 5-htmentioning

confidence: 99%

Frontiers of Serotonin Beyond the Brain

Maroteaux

Kilic

2019

Pharmacological Research

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Long time before its identification as 5-hydroxytryptamine (5-HT), the first described effect of serotonin was a cardiovascular action. At the end of 19th century, a substance present in serum, (thrombosed blood fraction), was found to act on heart and blood vessels: in 1896, Weiss showed that intravenous injection of serum into an animal caused an increase in breathing and cardiac frequencies, followed by a rapid decrease in blood pressure leading eventually to death [1]. In 1918, it was reported that citrated serum or blood platelet extract was vasoconstrictor, while uncoagulated blood or citrated plasma did not have a vasoconstrictor action [2]. In 1930, a substance, called enteramine, which contracted smooth muscles was isolated from intestinal enterochromaffin cells [3]. Finally, in late 1940s, a vasoconstrictor substance called serotonin was identified as 5-hydroxytryptamine [4, 5].

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Serotonin contribution to cardiac valve degeneration: new insights for novel therapies?

Cited by 24 publications

References 76 publications

Novel and atypical pathways for serotonin signaling

Novel and atypical pathways for serotonin signaling

Serotonin: a platelet hormone modulating cardiovascular disease

Frontiers of Serotonin Beyond the Brain

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