Adenosine Diphosphate Receptor P2Y12-Mediated Migration of Host Smooth Muscle-Like Cells and Leukocytes in the Development of Transplant Arteriosclerosis

Harada, Kosuke; Matsumoto, Yuji; Umemura, Kazuo

doi:10.1097/tp.0b013e318221d407

Cited by 28 publications

(25 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Migration facilitated by the activation of P2Y 2 receptors involved the ERK1/2 as well as the arrestin2 pathway [54,58]. Interestingly, migration induced by P2Y 12 receptor stimulation has been proposed to play a major role in transplant arteriosclerosis [57]. In agreement with that Fig.…”

Section: Discussionsupporting

confidence: 86%

“…α,β-methylene-ATP inhibited with a halfmaximal concentration of about 0.1 μM the migration of the cells. P2Y receptors including the P2Y 2 , P2Y 6 , and P2Y 12 subtypes mediate the opposite effect-an increase in migration [54][55][56][57][58][59]. Migration facilitated by the activation of P2Y 2 receptors involved the ERK1/2 as well as the arrestin2 pathway [54,58].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

P2X1 receptor-mediated inhibition of the proliferation of human coronary smooth muscle cells involving the transcription factor NR4A1

Hinze

Mayer

Harst

et al. 2013

Purinergic Signalling

View full text Add to dashboard Cite

Adenine nucleotides acting at P2X 1 receptors are potent vasoconstrictors. Recently, we demonstrated that activation of adenosine A 2B receptors on human coronary smooth muscle cells inhibits cell proliferation by the induction of the nuclear receptor subfamily 4, group A, member 1 (NR4A1; alternative notation Nur77). In the present study, we searched for long-term effects mediated by P2X 1 receptors by analyzing receptor-mediated changes in cell proliferation and in the expression of NR4A1. Cultured human coronary smooth muscle cells were treated with selective receptor ligands. Effects on proliferation were determined by counting cells and measuring changes in impedance. The induction of transcription factors was assessed by qPCR. The P2X receptor agonist α,β-methylene-ATP and its analog β,γ-methylene-ATP inhibited cell proliferation by about 50 % after 5 days in culture with half-maximal concentrations of 0.3 and 0.08 μM, respectively. The effects were abolished or markedly attenuated by the P2X 1 receptor antagonist NF449 (carbonylbis-imino-benzenetriylbis-(carbonylimino)tetrakis-benzene-1,3-disulfonic acid; 100 nM and 1 μM). α,β-methylene-ATP and β,γ-methylene-ATP applied for 30 min to 4 h increased the expression of NR4A1; NF449 blocked or attenuated this effect. Small interfering RNA directed against NR4A1 diminished the antiproliferative effects of α,β-methylene-ATP and β,γ-methylene-ATP. α,β-methylene-ATP (0.1 to 30 μM) decreased migration of cultured human coronary smooth muscle cells in a chamber measuring changes in impedance; NF449 blocked the effect. In conclusion, our results demonstrate for the first time that adenine nucleotides acting at P2X 1 receptors inhibit the proliferation of human coronary smooth muscle cells via the induction of the early gene NR4A1.

show abstract

Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

P2X1 receptor-mediated inhibition of the proliferation of human coronary smooth muscle cells involving the transcription factor NR4A1

Hinze

Mayer

Harst

et al. 2013

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…Several reviews discuss the use of anti-platelet drugs for the treatment and prevention of CAD [762,764,765]. It has been suggested that ADP-mediated migration of host smooth muscle-like cells and CD45 + leukocytes, via P2Y12R, may play a role in the development of transplant arteriosclerosis, partly by monocyte chemoattractant protein-1 [766]. Clinical trials with clopidogrel and ticlopidine in patients with CAD have shown significant benefit compared with aspirin.…”

Section: Coronary Artery Diseasementioning

confidence: 99%

Cardiac purinergic signalling in health and disease

Burnstock

Pelleg

2014

Purinergic Signalling

120

View full text Add to dashboard Cite

This review is a historical account about purinergic signalling in the heart, for readers to see how ideas and understanding have changed as new experimental results were published. Initially, the focus is on the nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory nerves, as well as in intracardiac neurons. Control of the heart by centers in the brain and vagal cardiovascular reflexes involving purines are also discussed. The actions of adenine nucleotides and nucleosides on cardiomyocytes, atrioventricular and sinoatrial nodes, cardiac fibroblasts, and coronary blood vessels are described. Cardiac release and degradation of ATP are also described. Finally, the involvement of purinergic signalling and its therapeutic potential in cardiac pathophysiology is reviewed, including acute and chronic heart failure, ischemia, infarction, arrhythmias, cardiomyopathy, syncope, hypertrophy, coronary artery disease, angina, diabetic cardiomyopathy, as well as heart transplantation and coronary bypass grafts.

show abstract

“…P2Y 12 −/− mice and mice treated with clopidogrel displayed reduced neointima formation in the wild-type grafted vessel with a reduction of infiltrating host-derived smooth musclelike cells and leukocytes. 10,41 Selective platelet depletion did not inhibit transplant atherosclerosis, suggesting involvement of the P2Y 12 receptors expressed on these host-derived smooth muscle-like cells and leukocytes, including DCs, possibly through a contribution to the migration of these cells.…”

Section: P2y 12 Receptor In Inflammationmentioning

confidence: 99%

“…8,9 The expression of the P2Y 12 receptor was long thought to be restricted to platelets and subregions of the brain. However, it has now been shown that this receptor is also expressed on vascular smooth muscle cells (VSMCs) 10,11 and dendritic cells (DCs). 12 On blood platelets, the P2Y 12 receptor is entirely responsible for the role played by ADP in the amplification of aggregation, secretion, and stabilization of platelet aggregates and in enhancement of the procoagulant activity induced by agonists, such as thrombin, collagen, or thromboxane A 2 .…”

Section: Platelet P2y 12 Receptormentioning

confidence: 99%

Purinergic Receptors in Thrombosis and Inflammation

Hechler

Gachet

2015

ATVB

146

101

View full text Add to dashboard Cite

Abstract-Under various pathological conditions, including thrombosis and inflammation, extracellular nucleotide levels may increase because of both active release and passive leakage from damaged or dying cells. Once in the extracellular compartment, nucleotides interact with plasma membrane receptors belonging to the P2 purinergic family, which are expressed by virtually all circulating blood cells and in most blood vessels. In this review, we focus on the specific role of the 3 platelet P2 receptors P2Y 1 , P2Y 12 , and P2X 1 in hemostasis and arterial thrombosis. Beyond platelets, these 3 receptors, along with the P2Y 2 , P2Y 6 , and P2X 7 receptors, constitute the main P2 receptors mediating the proinflammatory effects of nucleotides, which play important roles in various functions of circulating blood cells and cells of the vessel wall. Each of these P2 receptor subtypes specifically contributes to chronic or acute vascular inflammation and related diseases, such as atherosclerosis, restenosis, endotoxemia, and sepsis. The potential for therapeutic targeting of these P2 receptor subtypes is also discussed.

show abstract

Adenosine Diphosphate Receptor P2Y12-Mediated Migration of Host Smooth Muscle-Like Cells and Leukocytes in the Development of Transplant Arteriosclerosis

Abstract: Thus, the P2Y12-mediated migration of host-derived SMLCs and CD45+ leukocytes may play an important role in the development of TA, partly by MCP-1 pathways.

Cited by 28 publications

References 28 publications

P2X1 receptor-mediated inhibition of the proliferation of human coronary smooth muscle cells involving the transcription factor NR4A1

P2X1 receptor-mediated inhibition of the proliferation of human coronary smooth muscle cells involving the transcription factor NR4A1

Cardiac purinergic signalling in health and disease

Purinergic Receptors in Thrombosis and Inflammation

Contact Info

Product

Resources

About