Dataset Information

Platelet PI3K? Contributes to Carotid Intima-Media Thickening under Severely Reduced Flow Conditions.

ABSTRACT: Studies have begun to focus on the emerging function of platelets as immune and inflammatory cells that initiate and accelerate vascular inflammation. Phosphoinositide 3-kinase gamma (PI3K?) is critically involved in a number of inflammatory and autoimmune diseases. This study aims to investigate the contribution of platelet PI3K? to vascular remodeling under flow severely reduced conditions. Mouse partial left carotid artery ligation with adoptive transfer of activated, washed wild-type or PI3K?-/- platelets was used as the model. Intima-media area, leukocyte recruitment, and proinflammatory mediator expression were assessed. In vitro PI3K?-/- platelets were used to verify the effect of PI3K? on platelet activation, interaction with leukocytes, and endothelial cells. Mice injected with activated platelets showed a significant increase in intima-media thickening, recruitment of neutrophils (at 3 d) and macrophages (at 21 d), and intercellular adhesion molecule-1, vascular cell adhesion molecule-1, tumor necrosis factor alpha, and interleukin-6 expression (at 3 d) in the flow-reduced area. These effects were abrogated by platelet PI3K? deficiency. Circulating platelet-leukocyte aggregates were reduced in PI3K?-/- mice after partial ligation. In vivo data confirmed that PI3K? mediated Adenine di-Phosphate -induced platelet activation through the Akt and p38 MAP kinase signaling pathways. Moreover, platelet PI3K? deficiency reduced platelet-leukocyte aggregation and platelet-endothelial cell (EC) interaction. These findings indicate that platelet PI3K? contributes to platelet-mediated vascular inflammation and carotid intima-media thickening after flow severely reduced. Platelet PI3K? may be a new target in the treatment of vascular diseases.

SUBMITTER: Wang C

PROVIDER: S-EPMC4459692 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Platelet PI3Kγ Contributes to Carotid Intima-Media Thickening under Severely Reduced Flow Conditions.

Wang Cuiping C Jin Rong R Nanda Anil A Yan Jinchuan J Li Guohong G

PloS one 20150608 6

Studies have begun to focus on the emerging function of platelets as immune and inflammatory cells that initiate and accelerate vascular inflammation. Phosphoinositide 3-kinase gamma (PI3Kγ) is critically involved in a number of inflammatory and autoimmune diseases. This study aims to investigate the contribution of platelet PI3Kγ to vascular remodeling under flow severely reduced conditions. Mouse partial left carotid artery ligation with adoptive transfer of activated, washed wild-type or PI3K ...[more]

PMID: 26053836

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Project description:Background Helicobacter pylori (H. pylori) infection affects ≈4.4 billion people worldwide. Several studies suggest that this pathogen impacts the digestive system, causing diverse and severe conditions, and results in extragastrointestinal disorders like vascular diseases. Our study aims to examine the association between H. pylori infection and carotid intima-media thickness. Methods and Results Electronic databases (MEDLINE, Embase, CENTRAL, Web of Science, and Scopus) were searched for studies, comparing the thickness of the carotid intima-media in H. pylori-infected and noninfected individuals listed until October 20, 2020. Statistical analyses were performed using the random effects meta-analysis of model of weighted mean differences with the corresponding 95% CI using the DerSimonian and Laird method. The protocol was registered in advance in PROSPERO (International Prospective Register of Systematic Reviews; CRD42021224485). Thirteen studies were found meeting inclusion criteria for our systematic review and meta-analysis, presenting data on the thickness of the carotid intima-media considering the presence of H. pylori infection. Altogether, 2298 individuals' data were included (1360 H. pylori positive, 938 negative). The overall carotid intima-media thickness was significantly larger among infected patients compared with uninfected participants (weighted mean difference: 0.07 mm; 95% CI, 0.02-0.12; P=0.004; I2=91.1%; P<0.001). In case of the right common carotid artery, the intima-media thickening was found to be significant as well (weighted mean difference, 0.08 mm; 95% CI, 0.02-0.13, P=0.007; I2=85.1%; P<0.001), while it showed no significance in the left common carotid artery (weighted mean difference, 0.12 mm; 95% CI, -0.05 to 0.28, P=0.176; I2=97.4%; P<0.001). Conclusions H. pylori infection is associated with increased carotid intima-media thickness. Therefore, the infection may indirectly contribute to the development of major vascular events.

Project description:BackgroundIntima-media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.MethodsWe measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima-media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima-media thickness values.ResultsA total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima-media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima-media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima-media thickness of the internal carotid artery (7.6%, P<0.001) but not intima-media thickness of the common carotid artery (0.0%, P=0.99). With the presence of plaque, defined as intima-media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P=0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).ConclusionsThe maximum internal and mean common carotid-artery intima-media thicknesses both predict cardiovascular outcomes, but only the maximum intima-media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort. (Funded by the National Heart, Lung, and Blood Institute.).

Dataset Information

Platelet PI3K? Contributes to Carotid Intima-Media Thickening under Severely Reduced Flow Conditions.

Publications

Platelet PI3Kγ Contributes to Carotid Intima-Media Thickening under Severely Reduced Flow Conditions.

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