LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism

Carnevale, Roberto; Bartimoccia, Simona; Nocella, Cristina; Santo, Serena Di; Loffredo, Lorenzo; Illuminati, Giulio; Lombardi, Elisabetta; Boz, Valentina; Ben, Maria Del; Marco, Luigi De; Pignatelli, Pasquale

doi:10.1016/j.atherosclerosis.2014.08.041

Cited by 95 publications

(91 citation statements)

References 24 publications

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“…Isoprostanes, produced mainly through the non-enzymatic oxidation of arachidonic acid by reactive oxygen species, are recognized biomarkers of in vivo lipid peroxidation, and the production of isoprostanes is increased in the presence of oxidative stress [44]. An additional measure of oxidative stress is LDL-oxidation for also assessing lipid oxidation [45]. In the present study, we observed no effects on total 8-isoprostanes and LDLoxidation concentrations with consumption of the wild blueberry juice.…”

Section: Discussioncontrasting

confidence: 52%

The effects of 100% wild blueberry (Vaccinium angustifolium) juice consumption on cardiometablic biomarkers: a randomized, placebo-controlled, crossover trial in adults with increased risk for type 2 diabetes

et al. 2017

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Section: Discussioncontrasting

confidence: 52%

The effects of 100% wild blueberry (Vaccinium angustifolium) juice consumption on cardiometablic biomarkers: a randomized, placebo-controlled, crossover trial in adults with increased risk for type 2 diabetes

et al. 2017

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“…Studies by Terentis et al have demonstrated oxidation of tocopherol along with LDL oxidation early in lesion formation [131]. Several studies have proven that oxidative stress signaling is pathologically increased in many cell types involved in atherosclerosis, including platelets [132], endothelial cells [133], macrophages [134], and VSMC [129]. We have reported that increased oxidative stress is associated with vascular calcification in atherogenic ApoE −/− mice [122], [123].…”

Section: Regulation Of H2o2 Production In Vsmcmentioning

confidence: 57%

Redox signaling in cardiovascular pathophysiology: A focus on hydrogen peroxide and vascular smooth muscle cells

2016

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Oxidative stress represents excessive intracellular levels of reactive oxygen species (ROS), which plays a major role in the pathogenesis of cardiovascular disease. Besides having a critical impact on the development and progression of vascular pathologies including atherosclerosis and diabetic vasculopathy, oxidative stress also regulates physiological signaling processes. As a cell permeable ROS generated by cellular metabolism involved in intracellular signaling, hydrogen peroxide (H2O2) exerts tremendous impact on cardiovascular pathophysiology. Under pathological conditions, increased oxidase activities and/or impaired antioxidant systems results in uncontrolled production of ROS. In a pro-oxidant environment, vascular smooth muscle cells (VSMC) undergo phenotypic changes which can lead to the development of vascular dysfunction such as vascular inflammation and calcification. Investigations are ongoing to elucidate the mechanisms for cardiovascular disorders induced by oxidative stress. This review mainly focuses on the role of H2O2 in regulating physiological and pathological signals in VSMC.

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“…It has been shown that the injection of activated platelets in ApoE KO mice promotes leukocyte binding to endothelium and higher inflammation leading to exacerbation of atherosclerosis (41). Furthermore, activated platelets promote oxidative modification of LDL contributing to the accumulation of oxLDL, which in turn amplify platelet activation (42, 43). On the contrary, platelet hyporeactivity provides protection against atherosclerosis development (37, 44) and administration of, for example, aspirin and clopidogrel decreases platelet thrombus formation following rupture of atherosclerotic plaque in vivo (45).…”

Section: Discussionmentioning

confidence: 99%

Complete deletion of Cd39 is atheroprotective in apolipoprotein E-deficient mice

Giorgi

Enjyoji

Jiang

et al. 2017

Journal of Lipid Research

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Cd39 scavenges extracellular ATP and ADP, ultimately generating adenosine, a nucleoside, which has anti-inflammatory effects in the vasculature. We have evaluated the role of Cd39 in the development of atherosclerosis in hyperlipidemic mice. ApoE KO (Cd39+/+/ApoE−/−) and Cd39/ApoE double KO (DKO) (Cd39−/−/ApoE−/−) mice were maintained on chow or Western diet for up to 20 weeks before evaluation of atherosclerotic lesions. We found that DKO mice exhibited significantly fewer atherosclerotic lesions than ApoE KO mice, irrespective of diet. Analyses of plaque composition revealed diminished foam cells in the fatty streaks and smaller necrotic cores in advanced lesions of DKO mice, when compared with those in ApoE KO mice. This atheroprotective phenotype was associated with impaired platelet reactivity to ADP in vitro and prolonged platelet survival, suggesting decreased platelet activation in vivo. Further studies with either genetic deletion or pharmacological inhibition of Cd39 in macrophages revealed increased cholesterol efflux mediated via ABCA1 to ApoA1. This phenomenon was associated with elevated plasma HDL levels in DKO mice. Our findings indicate that complete deletion of Cd39 paradoxically attenuates development of atherosclerosis in hyperlipidemic mice. We propose that this phenotype occurs, at least in part, from diminished platelet activation, increased plasma HDL levels, and enhanced cholesterol efflux and indicates the complexity of purinergic signaling in atherosclerosis.

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LDL oxidation by platelets propagates platelet activation via an oxidative stress-mediated mechanism

Cited by 95 publications

References 24 publications

The effects of 100% wild blueberry (Vaccinium angustifolium) juice consumption on cardiometablic biomarkers: a randomized, placebo-controlled, crossover trial in adults with increased risk for type 2 diabetes

The effects of 100% wild blueberry (Vaccinium angustifolium) juice consumption on cardiometablic biomarkers: a randomized, placebo-controlled, crossover trial in adults with increased risk for type 2 diabetes

Redox signaling in cardiovascular pathophysiology: A focus on hydrogen peroxide and vascular smooth muscle cells

Complete deletion of Cd39 is atheroprotective in apolipoprotein E-deficient mice

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