Immune-mediated and lipid-mediated platelet function in atherosclerosis

Ahmadsei, Maiwand; Lievens, Dirk; Weber, Christian; Hundelshausen, Philipp von; Gerdes, Norbert

doi:10.1097/mol.0000000000000212

Cited by 18 publications

(12 citation statements)

References 196 publications

(133 reference statements)

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“…Moreover, these values were within the normal range according to respected values [ 28 , 29 ]. It is already known that platelets express and secrete inflammatory mediators (chemokines, sp-selectin, interleukin-1β, thromboxane, cytokines) and that elevated platelet counts were related to poor cardiovascular clinical outcomes [ 30 – 33 ]. The differences between groups and sequential changes in the platelet count and the mean platelet volume are summarized in Table 2 .…”

Section: Resultsmentioning

confidence: 99%

The effects of seed from Linum usitatissimum cultivar with increased phenylpropanoid compounds and hydrolysable tannin in a high cholesterol-fed rabbit

Króliczewska

Miśta

Ziarnik³

et al. 2018

Lipids Health Dis

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BackgroundDietary fat is considered one of the most important factors associated with blood lipid metabolism and plays a significant role in the cause and prevention of atherosclerosis that has been widely accepted as an inflammatory disease of the vascular system. The aim of the present study was to evaluate the effect of genetically modified flaxseed (W86) rich in phenylpropanoid compounds and hydrolysable tannin in high cholesterol-induced atherosclerosis rabbit models compared to parental cultivar Linola.MethodsTwenty-Eight White New Zealand white rabbits aged 6 months were randomly divided into four groups, control group, high cholesterol group (10 g/kg), Linola flaxseed group (100 g/kg) and W86 flaxseed group (100 g/kg). The rabbits were fed a normal diet or a high cholesterol diet for 10 weeks. Levels of blood lipids, hematological values, total antioxidative status and superoxide dismutase activity in serum were determined. Moreover, body weight and feed intake were measured after sixth and tenth weeks. After each stage of the experiment atherogenic indexes (non-HDL-C/HDL-C, LDL-C/HDL-C, and atherogenic index of plasma) was calculated.ResultsThe intake of a dyslipidaemic diet negatively influenced lipid profile in rabbits at the 10 weeks of feeding. W86 flaxseed significantly decreased total cholesterol, LDL-C, VLDL-C and TG serum levels in cholesterolemic rabbits compared with parental Linola after 10 weeks. Atherogenic indexes decreased over time with a significant difference between the diets and they were the best for W86 flaxseed. Similarly, the experimental addition of W86 significantly decreased atherogenic predictors such as heterophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and the mean platelet volume-to-lymphocyte ratio. In rabbits, W86 flaxseed increased the activity of superoxide dismutase and total antioxidative status compared to Linola.ConclusionsResults of the presented study suggest that the addition of W86 flaxseed alleviate serum lipid changes in high cholesterolemic diet-administered rabbits. W86 flaxseed significantly reduced atherogenic indexes, as compared with the Linola and indicate that W86 flaxseed more effectively red CVD risk factors during hypercholesterolemia. Moreover, the presented result suggested that W86 flaxseed can be a part of a heart-healthy and antiatherogenic diet for the human.Electronic supplementary materialThe online version of this article (10.1186/s12944-018-0726-4) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

The effects of seed from Linum usitatissimum cultivar with increased phenylpropanoid compounds and hydrolysable tannin in a high cholesterol-fed rabbit

Króliczewska

Miśta

Ziarnik³

et al. 2018

Lipids Health Dis

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“…86 Reducing cholesterol and circulating LDL levels affects platelet reactivity by cholesterol-dependent and pleiotropic, cholesterol-independent effects. 87 Clinically, pleiotropic, antithrombotic actions of statins have been concluded from the JUPITER trial that showed a significant reduction of deep vein thrombosis in the cohort treated with rosuvastatin. 88 Which molecular mechanisms lie behind these assumed antiplatelet effects have been investigated in preclinical studies.…”

Section: Sphingolipidsmentioning

confidence: 99%

Novel Approaches to Fine-Tune Therapeutic Targeting of Platelets in Atherosclerosis: A Critical Appraisal

2020

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The pathogenesis of atherosclerotic vascular disease is driven by a multitude of risk factors intertwining metabolic and inflammatory pathways. Increasing knowledge about platelet biology sheds light on how platelets take part in these processes from early to later stages of plaque development. Recent insights from experimental studies and mouse models substantiate platelets as initiators and amplifiers in atherogenic leukocyte recruitment. These studies are complemented by results from genetics studies shedding light on novel molecular mechanisms which provide an interesting prospect as novel targets. For instance, experimental studies provide further details how platelet-decorated von Willebrand factor tethered to activated endothelial cells plays a role in atherogenic monocyte recruitment. Novel aspects of platelets as atherogenic inductors of neutrophil extracellular traps and particularities in signaling pathways such as cyclic guanosine monophosphate and the inhibitory adaptor molecule SHB23/LNK associating platelets with atherogenesis are shared. In summary, it was our intention to balance insights from recent experimental data that support a plausible role for platelets in atherogenesis against a paucity of clinical evidence needed to validate this concept in humans.

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“…22 Platelet biology has been implicated in lipid metabolism and atherosclerosis, suggesting rs895953 could be affecting CAD risk through platelet-related pathways. 35,36…”

Section: Locus Associated With Tg and Hdl-c May Regulate Genes Affectmentioning

confidence: 99%

Bivariate GWAS scan identifies six novel loci associated with lipid levels and coronary artery disease

Voight

2018

Preprint

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Background-Plasma lipid levels are heritable and genetically associated with risk of coronary artery disease (CAD). However, genome-wide association studies (GWAS) routinely analyze these traits independently of one another. Joint GWAS for two related phenotypes can lead to a higher-powered analysis to detect variants contributing to both traits. Methods and Results-We performed a bivariate GWAS to discover novel loci associated with heart disease, using a CAD Meta-Analysis (122,733 cases and 424,528 controls), and lipid traits, using data from the Global Lipid Genetics Consortium (188,577 subjects). We identified six previously unreported loci at genome-wide significance (P < 5 x 10 -8 ), three which were associated with Triglycerides and CAD, two which were associated with LDL cholesterol and CAD, and one associated with Total Cholesterol and CAD. At several of our loci, the GWAS signals jointly localize with genetic variants associated with expression level changes for one or more neighboring genes, indicating that these loci may be affecting disease risk through regulatory activity. Conclusions-We discovered six novel variants individually associated with both lipids and coronary artery disease.

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Immune-mediated and lipid-mediated platelet function in atherosclerosis

Cited by 18 publications

References 196 publications

The effects of seed from Linum usitatissimum cultivar with increased phenylpropanoid compounds and hydrolysable tannin in a high cholesterol-fed rabbit

The effects of seed from Linum usitatissimum cultivar with increased phenylpropanoid compounds and hydrolysable tannin in a high cholesterol-fed rabbit

Novel Approaches to Fine-Tune Therapeutic Targeting of Platelets in Atherosclerosis: A Critical Appraisal

Bivariate GWAS scan identifies six novel loci associated with lipid levels and coronary artery disease

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