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http://purl.uniprot.org/citations/26988592http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26988592http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Platelets are important for the development and progression of atherosclerotic lesions. However, relatively little is known about the contribution of platelet signaling to this pathological process. Our recent work identified 2 independent, yet synergistic, signaling pathways that lead to the activation of the small GTPase Rap1; one mediated by the guanine nucleotide exchange factor, CalDAG-GEFI (CDGI), the other by P2Y12, a platelet receptor for adenosine diphosphate and the target of antiplatelet drugs. In this study, we evaluated lesion formation in atherosclerosis-prone low-density lipoprotein receptor deficient (Ldlr(-/-)) mice lacking CDGI or P2Y12 in hematopoietic cells.

Approach and results

Lethally irradiated Ldlr(-/-) mice were reconstituted with bone marrow from wild-type (WT), Caldaggef1(-/-) (cdgI(-/-)), p2y12(-/-), or cdgI(-/-)p2y12(-/-) (double knockout [DKO]) mice and fed a high-fat diet for 12 weeks. Ldlr(-/-) chimeras deficient for CDGI or P2Y12 developed significantly smaller atherosclerotic lesions in the aortic sinus and in aortas when compared with the Ldlr(-/-)/WT controls. We also observed a significant reduction in platelet-leukocyte aggregates in blood from hypercholesterolemic Ldlr(-/-)/cdgI(-/-) and Ldlr(-/-)/p2y12(-/-) chimeras. Consistently, fewer macrophages and neutrophils were detected in the aortic sinus of Ldlr(-/-)/cdgI(-/-) and Ldlr(-/-)/ p2y12(-/-) chimeras. Compared with controls, the plaque collagen content was significantly higher in Ldlr(-/-) chimeras lacking CDGI. Interestingly, no statistically significant additive effects were seen in Ldlr(-/-)/DKO chimeras when compared with chimeras lacking only CDGI.

Conclusions

Our findings suggest that CDGI is critical for atherosclerotic plaque development in hypercholesterolemic Ldlr(-/-) mice because of its contribution to platelet-leukocyte aggregate formation and leukocyte recruitment to the lesion area."xsd:string
http://purl.uniprot.org/citations/26988592http://purl.org/dc/terms/identifier"doi:10.1161/atvbaha.115.306347"xsd:string
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/author"Lee R.H."xsd:string
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/author"Bergmeier W."xsd:string
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/author"Conley P.B."xsd:string
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/author"Mackman N."xsd:string
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/author"Paul D.S."xsd:string
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/author"Beale A."xsd:string
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/author"Owens A.P."xsd:string
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/author"Boulaftali Y."xsd:string
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/author"Casari C."xsd:string
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/author"Piatt R."xsd:string
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/name"Arterioscler Thromb Vasc Biol"xsd:string
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/pages"792-799"xsd:string
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/title"CalDAG-GEFI Deficiency Reduces Atherosclerotic Lesion Development in Mice."xsd:string
http://purl.uniprot.org/citations/26988592http://purl.uniprot.org/core/volume"36"xsd:string
http://purl.uniprot.org/citations/26988592http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26988592
http://purl.uniprot.org/citations/26988592http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/26988592
http://purl.uniprot.org/uniprot/#_A0A0G2JGU7-mappedCitation-26988592http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26988592
http://purl.uniprot.org/uniprot/#_D3Z2F9-mappedCitation-26988592http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26988592
http://purl.uniprot.org/uniprot/#_D3YXD6-mappedCitation-26988592http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26988592
http://purl.uniprot.org/uniprot/#_A0A1L1SRE8-mappedCitation-26988592http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26988592
http://purl.uniprot.org/uniprot/#_D3Z3N3-mappedCitation-26988592http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26988592
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