Serotonin induces the expression of tissue factor and plasminogen activator inhibitor-1 in cultured rat aortic endothelial cells

Kawano, Hidehiko; Tsuji, Hajime; Nishimura, Hiromi; Kimura, Shinzo; Yano, Shingo; Ukimura, Naoki; Kunieda, Yasufumi; Yoshizumi, Masami; Sugano, Tomoko; Nakagawa, Keigo; Masuda, Haruchika; Sawada, Shohei; Nakagawa, Masao

doi:10.1182/blood.v97.6.1697

Cited by 53 publications

(30 citation statements)

References 40 publications

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“…Our data confirms this for ANSC. The 'trophic' activity of this neurotransmitter is also demonstrated in peripheral tissues, like in vascular smooth muscle cells (VSMC) where 5-HT remains a growth-modulating factor beyond the fetal period (Kawano et al, 2001). Recently, 5-HT has also been described as a survival factor of cardiomyocytes (Nebigil et al, 2003;Nebigil and Maroteaux, 2001).…”

Section: Discussionmentioning

confidence: 99%

Serotonin Depletion Hampers Survival and Proliferation in Neurospheres Derived from Adult Neural Stem Cells

Benninghoff¹,

Gritti²,

Rizzi³

et al. 2009

Neuropsychopharmacol

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Serotonin (5-HT) and the serotonergic system have recently been indicated as modulators of adult hippocampal neurogenesis. In this study, we evaluated the role of 5-HT on the functional features in neurospheres derived from adult neural stem cells (ANSC). We cultured neurospheres derived from mouse hippocampus in serum-free medium containing epidermal (EGF) and type-2 fibroblast growth factor (FGF2). Under these conditions ANSC expressed both isoforms of tryptophane-hydroxylase (TPH) and produced 5-HT. Blocking TPH function by para-chlorophenylalanine (PCPA) reduced ANSC proliferation, which was rescued by exogenous 5-HT. 5-HT action on ANSC was mediated predominantly by the serotonin receptor subtype 5-HT1A and, to a lesser extent, through the 5-HT2C (receptor) subtype, as shown by selectively antagonizing these receptors. Finally, we documented a 5-HT-induced increase of ANSC migration activity. In summary, we demonstrated a powerful serotonergic impact on ANSC functional features, which was mainly mediated by 5-HT1A receptors.

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Section: Discussionmentioning

confidence: 99%

Serotonin Depletion Hampers Survival and Proliferation in Neurospheres Derived from Adult Neural Stem Cells

Benninghoff¹,

Gritti²,

Rizzi³

et al. 2009

Neuropsychopharmacol

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“…The existence of endothelial 5-HT 2A receptors was reported but there is little work about the expression of 5-HT 2A receptors in endothelium (31). On the other hand, a 5-HT 2A receptor antagonist showed endothelium-dependent vasodilatation via 5-HT 1 -like or 5-HT 2B receptors (42) and angiogenesis via the 5-HT 1B /Akt/eNOS pathway in diabetic mice (43).…”

Section: Discussionmentioning

confidence: 99%

“…by inhibiting the activity of tissue plasminogen activator (31). The endothelium-dependent relaxation (EDR) induced by high glucose is improved by 5-HT 2A receptor antagonists in isolated rat aorta by decreasing superoxide anion (O 2 − ) production and by increasing superoxide dismutase (SOD) activity and nitric oxide (NO) release (32).…”

Section: Discussionmentioning

confidence: 99%

Serotonin Potentiates High-Glucose^|^ndash;Induced Endothelial Injury: the Role of Serotonin and 5-HT2A Receptors in Promoting Thrombosis in Diabetes

Yamada¹,

Niki²,

Nagai³

et al. 2012

J Pharmacol Sci

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Abstract. To clarify the involvement of 5-hydroxytryptamine (5-HT) in promotion of thrombogenesis in diabetes, we examined the inhibitory effect of sarpogrelate, a 5-HT 2A receptor antagonist, on thrombus formation in diabetic rats. In streptozotocin-induced diabetic rats, polyethylene tubeinduced thrombus formation was enhanced compared with that in normal rats. The thrombogenesis was inhibited by sarpogrelate; cilostazol, a PDE3 inhibitor; and aspirin, a COX inhibitor, by 75.8%, 42.3%, and 34.3%, respectively. The inhibition by sarpogrelate was more pronounced in diabetic rats than normal ones. High glucose and 5-HT increased the expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and combination of both high glucose and 5-HT further potentiated the effect. Sarpogrelate but not aspirin inhibited the increase in VCAM-1 expression induced by high glucose and 5-HT. These findings suggest that 5-HT mediates the enhanced thrombogenesis in diabetes and suggests that a 5-HT 2A receptor antagonist may have novel therapeutic potential for the treatment of diabetic complications.

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“…Endothelial TF is induced by cytokines such as tumor necrosis factor-␣ (TNF-␣), 6 interleukin-1␤, 7 or CD40 ligand, 8 by biogenic amines such as serotonin 9 or histamine, 10 and by mediators such as thrombin, oxidized LDL, or vascular endothelial growth factor (Figure 2). [11][12][13] Despite their diversity, most of these mediators share similar signal transduction pathways regulating TF induction.…”

Section: Endothelial Cellsmentioning

confidence: 99%

Tissue Factor in Cardiovascular Diseases

2006

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Abstract-Tissue factor (TF), formerly known as thromboplastin, is the key initiator of the coagulation cascade; it binds factor VIIa resulting in activation of factor IX and factor X, ultimately leading to fibrin formation. TF expression and activity can be induced in endothelial cells, vascular smooth muscle cells, and monocytes by various stimuli such as cytokines, growth factors, and biogenic amines. These mediators act through diverse signal transduction mechanisms including MAP kinases, PI3-kinase, and protein kinase C. Cellular TF is present in three pools as surface, encrypted, and intracellular protein. TF can also be detected in the bloodstream, referred to as circulating or blood-borne TF. Elevated levels of TF are observed in patients with cardiovascular risk factors such as hypertension, diabetes, dyslipidemia, and smoking as well as in those with acute coronary syndromes. TF may indeed be involved in the pathogenesis of atherosclerosis by promoting thrombus formation; in addition, it can induce migration and proliferation of vascular smooth muscle cells. As a consequence, therapeutic strategies have been developed to specifically interfere with the action of TF such as antibodies against TF, site-inactivated factor VIIa, or recombinant TF pathway inhibitor.

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Serotonin induces the expression of tissue factor and plasminogen activator inhibitor-1 in cultured rat aortic endothelial cells

Cited by 53 publications

References 40 publications

Serotonin Depletion Hampers Survival and Proliferation in Neurospheres Derived from Adult Neural Stem Cells

Serotonin Depletion Hampers Survival and Proliferation in Neurospheres Derived from Adult Neural Stem Cells

Serotonin Potentiates High-Glucose^|^ndash;Induced Endothelial Injury: the Role of Serotonin and 5-HT2A Receptors in Promoting Thrombosis in Diabetes

Tissue Factor in Cardiovascular Diseases

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