scholarly journals Altered microRNA expression profles are involved in Storage Lesions of Apheresis Platelet

2018 ◽  
Author(s):  
Zhaohu Yuan ◽  
Qianyu Wu ◽  
Xiaojie Chen ◽  
Yaming Wei
Keyword(s):  
Platelet Aggregation ◽  
Signaling Pathway ◽  
Platelet Reactivity ◽  
Human Platelets ◽  
Reactivity Index ◽  
Pdgf Receptor ◽  
Receptor Signaling ◽  
Storage Lesion ◽  
Mirna Array ◽  
Receptor Signaling Pathway

ABSTRACTAlthough platelet is anucleate cell, it contains a large amount miRNAs. This study aims to explore the relationship between miRNAs expression profles and platelets function, as well as miRNAs potential roles during platelet storage lesions. Platelets were collected from 15 healthy men with O blood types. MiRNAs profiles in platelets were detected by Agilent Human miRNA Array Differential miRNA levels were studied using human platelets after apheresis and stored for 2, 5 and 8 days using microarray. There were 167 and 230 altered miRNAs during the 5 and 8 day storage, respectively. In addition, the number of reduced miRNAs was much greater than that of increased. And many of them are involved in functions of platelet activation, degranulation, PDGF receptor signaling pathway and cell differentiation. The results of RT-PCR showed that the expression of miR-21-5p, miR-21-3p and miR-155 decreased on the 5th day, while miR-223, miR-3162 and let-7b increased. Flow cytometry results revealed that with increase of storage time, the expression of P2Y12 increased and phosphorylation level of VASP reduced. Meanwhile, the platelet reactivity index (PRI) decreased from 72.7% to 18.2%, while the apoptotic percentage of platelet significantly increased. For the first time, we found altered miRNAs are closely related to platelet aggregation, including P2Y12, VASP and GPⅡb/Ⅲa. Through KEGG database prediction, we verified there were many miRNAs impacting the pathway of platelet aggregation, such as miR-223, miR-21 and let-7b, which indicated miRNAs might serve as potential biomarkers of storage lesion in platelet. These target miRNAs are related to activation, degranulation and PDGF receptor signaling pathway of platelet.

Interactions Between Blood Platelets and Vascular Endothelium in vitro Studies

1979 ◽  
Author(s):  
M.A. Gimbrone ◽  
K.D. Curwen ◽  
R. I. Handin
Keyword(s):  
Platelet Aggregation ◽  
Vascular Endothelium ◽  
Potent Inhibitor ◽  
Platelet Reactivity ◽  
Blood Platelets ◽  
Primary Cultures ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Platelet Adherence

Endothelial cells (EC) can actively influence the hemostatic response at sites of vascular injury through multiple mechanisms. For example, EC can degrade adenosine diphosphate, release plasminogen activator, and synthesize prostacyclin (PGI2), a potent inhibitor of platelet aggregation. We have examined whether PGI2 also might account for the normal lack of platelet adherence to the uninjured EC surface. In a monolayer adherence assay, radiolabeled human platelets in citrated plasma showed minimal interaction with primary cultures of human EC (<1 platelet adhering per cell). Platelets from aspirin-treated and untreated donors behaved similarly. However, aspirin pretreatment of EC consistently resulted in ~2-fold increases in platelet adherence which could be completely abolished by exogenous PGI2 (0.5–1.0 μg/ml). SV40-transformed human EC (SVHEC), which are deficient in PGI2 production compared to primary EC, showed 10-30 times more platelet adherence. Exogenous PGI2 produced a dose - related (.001-1.0 μg/ml) decrease in platelet adherence to SVHEC but did not result in the basal levels observed with normal EC monolayers. These data suggest that : 1) In addition to its effects on platelet aggregation, PGI2 can influence platelet endothelial cell interactions; 2) The increased platelet reactivity of transformed EC is associated with, but not completely attributable, to decreased PGI2 production; and 3) Factors other than PGI2 may play a role in the thromboresistance of normal vascular endothelium.

scholarly journals A comprehensive contribution of genes for aryl hydrocarbon receptor signaling pathway to hypertension susceptibility

2017 ◽  
Vol 27 (2) ◽  
pp. 57-69 ◽  
Author(s):  
Alexey V. Polonikov ◽  
Olga Yu. Bushueva ◽  
Irina V. Bulgakova ◽  
Maxim B. Freidin ◽  
Mikhail I. Churnosov ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Signaling Pathway ◽  
Receptor Signaling ◽  
Aryl Hydrocarbon ◽  
Receptor Signaling Pathway

Cross-talk between an activator of nuclear receptors-mediated transcription and the D1 dopamine receptor signaling pathway

2005 ◽  
Vol 80 (3) ◽  
pp. 379-385 ◽  
Author(s):  
Azriel Schmidt ◽  
Robert Vogel ◽  
Su Jane Rutledge ◽  
Evan E. Opas ◽  
Gideon A. Rodan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Dopamine Receptor ◽  
Nuclear Receptors ◽  
Cross Talk ◽  
Receptor Signaling ◽  
D1 Dopamine Receptor ◽  
Receptor Signaling Pathway

Neuromedin U-induced anorexigenic action is mediated by the corticotropin-releasing hormone receptor-signaling pathway in goldfish

Peptides ◽  
2009 ◽  
Vol 30 (12) ◽  
pp. 2483-2486 ◽  
Author(s):  
Keisuke Maruyama ◽  
Kohei Wada ◽  
Kotaro Ishiguro ◽  
Sei-Ichi Shimakura ◽  
Tatsuya Wakasugi ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hormone Receptor ◽  
Receptor Signaling ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Receptor Signaling Pathway

Zinc oxide nanoparticle disruption of store-operated calcium entry in a muscarinic receptor signaling pathway

2010 ◽  
Vol 24 (7) ◽  
pp. 1953-1961 ◽  
Author(s):  
Hsiu-Jen Wang ◽  
Anna C. Growcock ◽  
Tso-hao Tang ◽  
Jennifer O’Hara ◽  
Yue-wern Huang ◽  
...  
Keyword(s):  
Zinc Oxide ◽  
Signaling Pathway ◽  
Muscarinic Receptor ◽  
Calcium Entry ◽  
Receptor Signaling ◽  
Zinc Oxide Nanoparticle ◽  
Store Operated Calcium Entry ◽  
Receptor Signaling Pathway ◽  
Oxide Nanoparticle

scholarly journals Lipid Receptor GPR31 (G-Protein–Coupled Receptor 31) Regulates Platelet Reactivity and Thrombosis Without Affecting Hemostasis

2020 ◽  
Author(s):  
Layla Van Doren ◽  
Nga Nguyen ◽  
Christopher Garzia ◽  
Elizabeth Fletcher ◽  
Ryan Stevenson ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Carotid Artery ◽  
G Protein ◽  
Arterial Thrombosis ◽  
Platelet Reactivity ◽  
Human Platelets ◽  
Calcium Flux ◽  
G Protein Coupled Receptor ◽  
Carotid Artery Injury ◽  
G Protein Coupled

Objective: 12-LOX (12-lipoxygenase) produces a number of bioactive lipids including 12(S)-HETE that are involved in inflammation and platelet reactivity. The GPR31 (G-protein–coupled receptor 31) is the proposed receptor of 12(S)-HETE; however, it is not known whether the 12(S)-HETE-GPR31 signaling axis serves to enhance or inhibit platelet activity. Approach and Results: Using pepducin technology and biochemical approaches, we provide evidence that 12(S)-HETE-GPR31 signals through Gi to enhance PAR (protease-activated receptor)-4–mediated platelet activation and arterial thrombosis using both human platelets and mouse carotid artery injury models. 12(S)-HETE suppressed AC (adenylyl cyclase) activity through GPR31 and resulted in Rap1 and p38 activation and low but detectable calcium flux but did not induce platelet aggregation. A GPR31 third intracellular (i3) loop–derived pepducin, GPR310 (G-protein–coupled receptor 310), significantly inhibited platelet aggregation in response to thrombin, collagen, and PAR4 agonist, AYPGKF, in human and mouse platelets but relative sparing of PAR1 agonist SFLLRN in human platelets. GPR310 treatment gave a highly significant 80% protection ( P =0.0018) against ferric chloride–induced carotid artery injury in mice by extending occlusion time, without any effect on tail bleeding. PAR4-mediated dense granule secretion and calcium flux were both attenuated by GPR310. Consistent with these results, GPR310 inhibited 12(S)-HETE–mediated and PAR4-mediated Rap1-GTP and RASA3 translocation to the plasma membrane and attenuated PAR4-Akt and ERK activation. GPR310 caused a right shift in thrombin-mediated human platelet aggregation, comparable to the effects of inhibition of the Gi-coupled P2Y 12 receptor. Co-immunoprecipitation studies revealed that GPR31 and PAR4 form a heterodimeric complex in recombinant systems. Conclusions: The 12-LOX product 12(S)-HETE stimulates GPR31-Gi–signaling pathways, which enhance thrombin-PAR4 platelet activation and arterial thrombosis in human platelets and mouse models. Suppression of this bioactive lipid pathway, as exemplified by a GPR31 pepducin antagonist, may provide beneficial protective effects against platelet aggregation and arterial thrombosis with minimal effect on hemostasis.

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