ArticleArteriosclerosis, thrombosis, and vascular biology2016
CalDAG-GEFI Deficiency Reduces Atherosclerotic Lesion Development in Mice.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Immunothrombosis in neurovascular disease.Research and practice in thrombosis and haemostasis · 2024Article
- The Emerging Role of Rho Guanine Nucleotide Exchange Factors in Cardiovascular Disorders: Insights Into Atherosclerosis: A Mini Review.Frontiers in cardiovascular medicine · 2021Review
- Targeting Platelet in Atherosclerosis Plaque Formation: Current Knowledge and Future Perspectives.International journal of molecular sciences · 2020Review
- The role of P2Y12 receptor inhibition in ischemic stroke on microglia, platelets and vascular smooth muscle cells.Journal of thrombosis and thrombolysis · 2020Review
- RasGRP2 Structure, Function and Genetic Variants in Platelet Pathophysiology.International journal of molecular sciences · 2020Review
- RAP GTPases and platelet integrin signaling.Platelets · 2019Review
- Platelets Are at the Nexus of Vascular Diseases.Frontiers in cardiovascular medicine · 2019Review
- The role of P2YCellular and molecular life sciences : CMLS · 2019Review
- Reporting Sex and Sex Differences in Preclinical Studies.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Platelet Signaling Pathways and New Inhibitors.Arteriosclerosis, thrombosis, and vascular biology · 2018Review
- Dual Anticoagulant and Antiplatelet Therapy for Coronary Artery Disease and Peripheral Artery Disease Patients.Arteriosclerosis, thrombosis, and vascular biology · 2018Review
- Translational Implications of Platelets as Vascular First Responders.Circulation research · 2018Review
- Phenotype analysis and clinical management in a large family with a novel truncating mutation inResearch and practice in thrombosis and haemostasis · 2017Article
- Integrin signaling in atherosclerosis.Cellular and molecular life sciences : CMLS · 2017Review
- Losing your GRP on platelet activation.Blood · 2016Article
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Authors and funding
10 authors.
Funding
Abstract
objectivePlatelets 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
resultsLethally 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.
conclusionsOur 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.
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