Mitogenic effect of serotonin on vascular endothelial cells.

Pakala, Rajbabu; Willerson, J T; Benedict, Claude R.

doi:10.1161/01.cir.90.4.1919

Cited by 121 publications

(79 citation statements)

References 46 publications

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“…P values less than 0.05 were regarded as significant. [7,8]. In the present study, 5-HT at lower concentrations (nM order) increased migration of HAECs through 5HT 1 receptor stimulation.…”

Section: Discussionsupporting

confidence: 52%

“…However, there have been no studies on 5-HT action on migration of vascular endothelial cells except for one study that showed that 5-HT inhibited movement of bovine aortic endothelial cells as evaluated by cell phagokinesis [6]. On the other hand, 5-HT has been reported to potentiate proliferation of vascular endothelial cells [7,8], although the mechanism involved in this 5-HT action remains to be determined. The purpose of the present study was to investigate whether 5-HT affects movement of human vascular endothelial cells (HAECs) by using time-lapse microscopy, a sensitive method to evaluate cell motility.…”

Section: Introductionmentioning

confidence: 99%

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5‐Hydroxytryptamine as a potent migration enhancer of human aortic endothelial cells

Matsusaka

Wakabayashi

2005

FEBS Letters

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The purpose of the present study was to investigate whether 5-hydroxytryptamine (5-HT, serotonin) affects migration of vascular endothelial cells. 5-HT significantly enhanced migration of human aortic endothelial cells (HAECs), and this enhancement was completely inhibited by GR 55562, a 5-HT 1 receptor antagonist, and fluoxetine, a 5-HT transporter inhibitor, but was not affected by ketanserin, a 5-HT 2 receptor antagonist. 5-HT stimulation increased RhoA and ERK activity of HAECs, and inhibitors of RhoA (Y-27632 and H-1152) and inhibitors of MEK (U0126 and PD98059) abolished the 5-HTinduced increase in migration velocity. Inhibition of Rho kinase by Y-27632 blocked stress fiber formation and rear release of HAECs. Thus, 5-HT has a potent enhancing action on migration of HAECs through activating the RhoA and ERK pathways following 5-HT 1 receptor stimulation.

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“…P values less than 0.05 were regarded as significant. [7,8]. In the present study, 5-HT at lower concentrations (nM order) increased migration of HAECs through 5HT 1 receptor stimulation.…”

Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

5‐Hydroxytryptamine as a potent migration enhancer of human aortic endothelial cells

Matsusaka

Wakabayashi

2005

FEBS Letters

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“…However, stimulation of proliferation is one of the well known actions of serotonin in non-neuronal tissues (43)(44)(45)(46)(47)(48). Osteocytes, which represent the highest differentiation stage of the osteoblastic lineage, do not proliferate (49) and therefore cannot be used in a proliferation assay.…”

Section: Resultsmentioning

confidence: 99%

“…A third area in which serotonin has been found active is that of regulation of proliferation of cells of various origin via the 5-HT 2A receptor (39,43,44,46), as well as via the 5-HT 2B receptor (45,48). In the present study, we have shown that bone cells express not only serotonin receptor mRNA, but also contain active receptors by demonstrating that serotonin or rather its more 5-HT 2 receptor-selective analog ␣-methyl-5-HT (31), could stimulate proliferation of PF.…”

Section: Discussionmentioning

confidence: 99%

Expression of Serotonin Receptors in Bone

Westbroek¹,

Plas²,

Rooij³

et al. 2001

Journal of Biological Chemistry

190

138

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The 5-hydroxytryptamine (5-HT) receptors 5-HT 2A , 5-HT 2B , and 5-HT 2C belong to a subfamily of serotonin receptors. Amino acid and mRNA sequences of these receptors have been published for several species including man. The 5-HT 2 receptors have been reported to act on nervous, muscle, and endothelial tissues. Here we report the presence of 5-HT 2B receptor in fetal chicken bone cells. 5-HT 2B receptor mRNA expression was demonstrated in osteocytes, osteoblasts, and periosteal fibroblasts, a population containing osteoblast precursor cells. Pharmacological studies using several agonists and antagonists showed that occupancy of the 5-HT 2B receptor stimulates the proliferation of periosteal fibroblasts. Activity of the 5-HT 2A receptor could however not be excluded. mRNA for both receptors was shown to be equally present in adult mouse osteoblasts. Osteocytes, which showed the highest expression of 5-HT 2B receptor mRNA in chicken, and to a lesser extent osteoblasts, are considered to be mechanosensor cells involved in the adaptation of bone to its mechanical usage. Nitric oxide is one of the signaling molecules that is released upon mechanical stimulation of osteocytes and osteoblasts. The serotonin analog ␣-methyl-5-HT, which preferentially binds to 5-HT 2 receptors, decreased nitric oxide release by mechanically stimulated mouse osteoblasts. These results demonstrate that serotonin is involved in bone metabolism and its mechanoregulation.The main highly differentiated cell types in bone tissue are the osteoclast, the osteoblast (OB), 1 and the osteocyte (OCY). Osteoclasts are multinucleated cells of hemopoietic origin and are related to the monocyte/macrophage (1, 2, 3). Osteoblasts on the other hand are of mesenchymal stock. Their stem and progenitor cells are present in the periosteum, endosteum, and bone marrow stroma (4). Osteocytes differentiate from osteoblasts. During the process of bone formation, a number of cells from the osteoblast layer is encapsulated in the newly formed bone matrix, whereas the other cells retract with the bone formation front. The cells that are incorporated in the bone matrix change from a cuboidal into a more stellate-shaped morphology and become osteocytes. The result of this process is a three-dimensional cellular network of osteocytes within the mineralized matrix connected to each other and to the bone surface cells by thin cell processes (5).Together these three cell types produce, maintain, and adapt or repair, if necessary, the mineralized bone matrix. Osteoclasts are capable of bone resorption, osteoblasts of bone formation. The function of osteocytes is less well understood. Because of their location within the bone matrix, osteocytes are in a prime position for the detection of mechanical inadequacies of the tissue. They are believed to act as sensor cells that translate mechanical stimuli resulting from gravitational and muscular forces on the skeleton into biochemical signals. These biochemical signals in turn activate the effectors of bone turnover, osteoclasts...

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“…One of those substances is thromboxane A2, a powerful vasoconstrictor whose production is high in PAH patients 41 . Serotonin and growth factors, such as PDGF, EGF and TGF-α, are also released, with mitogenic effect on vascular smooth muscle cells, fibroblasts and endothelial cells 42 .…”

Section: Platelets and Serotoninmentioning

confidence: 99%

Hipertensão arterial pulmonar: fisiopatologia, aspectos genéticos e resposta ao uso crônico do sildenafil

Barreto¹,

Franchi²,

Pereira³

et al. 2005

Arq. Bras. Cardiol.

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Mitogenic effect of serotonin on vascular endothelial cells.

Abstract: 5-HT is a mitogen for endothelial cells at concentrations likely to be present at sites of vascular injury. This effect is probably mediated via the 5-HT2 receptor. The growth-promoting effects of 5-HT on endothelial cells may facilitate the healing of intima after vascular damage.

Cited by 121 publications

References 46 publications

5‐Hydroxytryptamine as a potent migration enhancer of human aortic endothelial cells

5‐Hydroxytryptamine as a potent migration enhancer of human aortic endothelial cells

Expression of Serotonin Receptors in Bone

Hipertensão arterial pulmonar: fisiopatologia, aspectos genéticos e resposta ao uso crônico do sildenafil

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