The role of cytokines in the development of atherosclerosis

Fatkhullina, Aliia R.; Peshkova, Iuliia O.; Koltsova, Ekaterina K.

doi:10.1134/s0006297916110134

Cited by 237 publications

(197 citation statements)

References 112 publications

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“…Inflammation and oxidative stress are key factors at all stages of development of atherosclerosis . The origin of the atherosclerotic plaque is initiated and sustained by the combined endothelial dysfunction caused by chronic exposure to factors that promote vascular inflammation, such as hyperlipidemia, hypertension, smoking, and diabetes .…”

Section: Discussionmentioning

confidence: 99%

Chia (Salvia hispanica L.) Seed Total Protein and Protein Fractions Digests Reduce Biomarkers of Inflammation and Atherosclerosis in Macrophages In Vitro

Grancieri

Martino

Mejía

2019

Molecular Nutrition Food Res

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Scope The objectives are to evaluate the anti‐inflammatory and anti‐atherosclerotic effects of digested total protein and digested protein fractions from chia seed in macrophages in vitro. Methods and results Total protein and protein fractions (albumin, globulin, glutelin, and prolamin) are isolated from chia seed and digested using simulated gastrointestinal conditions, resulting in digested total protein (DTP) and digested protein fractions (DPF). DTP and DPF are applied (1.0 mg mL−1) in RAW 264.4 macrophages stimulated with LPS (1 µg mL−1) for inflammation or ox‐LDL (80 µg mL−1) for atherosclerosis. In the inflammatory process, DTP and DPF reduce p‐NF‐κB, iNOS, p‐JNK, and AP‐1. Digested glutelin reduces the secretion of nitric oxide (65.1%), reactive oxygen species (19.7%), prostaglandins (34.6%), TNF‐α (24.1%), MCP‐1 (18.9%), IL‐6 (39.6%), and IL‐10 (68.7%). DTP and DPF reduce the NF‐κB translocation to nuclei. DTP and digested glutelin reduce iCAM expression (86.4%, 80.8%), LOX‐1 (37.3%, 35.7%), iNOS (67.0%, 42.2%), and NF‐κB (57.5%, 71.1%). DTP is effective in reducing secretion of nitric oxide (43.4%), lipid accumulation (41.9%), prostaglandins (41.9%), TNF‐α (43.3%), MCP‐1 (47.6%), and IL‐6 (50.5%). Peptides from chia DTP and DPF are also characterized. Conclusion DTP and digested glutelin from chia seed reduce expression and secretion of markers related to inflammation and atherosclerosis pathways.

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Section: Discussionmentioning

confidence: 99%

Chia (Salvia hispanica L.) Seed Total Protein and Protein Fractions Digests Reduce Biomarkers of Inflammation and Atherosclerosis in Macrophages In Vitro

Grancieri

Martino

Mejía

2019

Molecular Nutrition Food Res

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“…The crucial role of pro-inflammatory cytokines (e.g., MCP-1, TNF-α and IL-6) in the initiation and progression of AT is well documented [8, 28, 65-67]. However, there are many challenges when studying the immune system in mice aortic tissues, due to the size and the number of cells obtained from the aorta.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that MCP-1 plays an important role in the recruitment and trans-endothelial migration of monocytes in early atherogenesis [1, 71, 72]. At the same time, IL-6 is an important biomolecule that increases the oxidative stress, promotes fatty streaks and induces leukocytes recruitment into the sub-endothelial space [65, 73]. This led us to propose that the reduction of pro-inflammatory mediators by sildenafil might be justified by an increase in cGMP.…”

Section: Discussionmentioning

confidence: 99%

“…Confirming our previous observations, the new finding in this issue is that treatment with sildenafil shifted the exacerbated contractile response to TP and ET-1 close to that exhibited by normal wild-type animals. These responses can be explained by three main factors: 1) normalization of [Ca +2 ] c in smooth vascular muscle cells by increasing cGMP, correcting this abnormal pathway; 2) reduction of levels •O 2 -, restoring the bioavailability of NO and lastly (and most surprisingly) the reduction of proinflammatory IL-6, TNF-α and MCP-1 (important stimulators of ROS) [8, 19, 65-67]. In addition to the data relating to changes in vascular inflammatory cytokines, we are demonstrating, for the first time, evidence of an anti-inflammatory effect of sildenafil in atherosclerotic apoE -/- mice (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Sildenafil (Viagra®) Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

Leal

Dias

Porto³

et al. 2017

Cell Physiol Biochem

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Background/Aims: The atherosclerotic apolipoprotein E-deficient (apoE^-/-) mouse exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The objectives of this study were: a) to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2), thromboxane A2 (TXA2) and endothelin-1 (ET-1) to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b) to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction. Methods: Adult male apoE^-/- mice were treated with sildenafil (40 mg/kg/day, for 3 weeks) and compared with non-treated ApoE^-/- and wild-type mice. The beneficial effects of sildenafil on vascular contractile response to phenylephrine (PE) in aortic rings were evaluated before and after incubation with Cox-1 (SC-560) or Cox-2 (NS-398) inhibitors or the TP antagonist SQ-29548, and on contractile responsiveness to ET-1. Results: ApoE^-/- mice exhibited enhanced vasoconstriction to PE (R_max ∼35%, p<0.01), which was prevented by treatment with sildenafil. The enhanced PE-induced contractions were abolished by both Cox-1 inhibition and TP antagonist, but were not modified by Cox-2 inhibition. Aortic rings from ApoE^-/- mice also exhibited enhanced contractions to ET-1 (R_max ∼30%, p<0.01), which were attenuated in sildenafil-treated ApoE^-/- mice. In addition, we observed augmented levels of vascular proinflammatory cytokines in ApoE^-/- mice, which were partially corrected by treatment with sildenafil (IL-6, IL-10/IL-6 ratio and MCP-1). Conclusion: The present data show that the Cox-1/TXA2 pathway prevails over the Cox-2 isoform in the mediation of vascular hypercontractility observed in apoE^-/-mice. The results also show a beneficial effect of sildenafil on this endothelial dysfunction and on the proinflammatory cytokines in atherosclerotic animals, opening new perspectives for the treatment of other endothelium-related cardiovascular abnormalities.

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“…Atherosclerosis is a common inflammatory vascular disease worldwide, which is associated with high morbidity and mortality . Endothelial cell dysfunction and damage evoked by reactive oxygen species (ROS) is central in the pathogenesis of atherosclerosis .…”

Section: Introductionmentioning

confidence: 99%

Secreted frizzled‐related protein 5 protects against oxidative stress‐induced apoptosis in human aortic endothelial cells via downregulation of Bax

Wang

Peng

Jiang

et al. 2017

J Biochem & Molecular Tox

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This study was undertaken to determine the role of secreted frizzled-related protein 5 (SFRP5) in endothelial oxidative injury. Human aortic endothelial cells (HAECs) were exposed to different oxidative stimuli and examined for SFRP5 expression. The effects of SFRP5 overexpression and knockdown on cell viability, apoptosis, and reactive oxygen species production were measured. HAECs treated with angiotensin (Ang) II (1 μM) or oxidized low-density lipoprotein (oxLDL) (150 μg/mL) showed a significant increase in SFRP5 expression. Overexpression of SFRP5 significantly attenuated the viability suppression and apoptosis induction by Ang II and oxLDL, whereas the knockdown of SFRP5 exerted opposite effects. Overexpression of SFRP5 prevented ROS formation and β-catenin activation and reduced Bax expression. Co-expression of Bax significantly reversed the anti-apoptotic effect of SFRP5 overexpression, whereas knockdown of Bax restrained Ang II- and oxLDL-induced apoptosis in HAECs. Taken together, SFRP5 confers protection against oxidative stress-induced apoptosis through inhibition of β-catenin activation and downregulation of Bax.

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The role of cytokines in the development of atherosclerosis

Cited by 237 publications

References 112 publications

Chia (Salvia hispanica L.) Seed Total Protein and Protein Fractions Digests Reduce Biomarkers of Inflammation and Atherosclerosis in Macrophages In Vitro

Chia (Salvia hispanica L.) Seed Total Protein and Protein Fractions Digests Reduce Biomarkers of Inflammation and Atherosclerosis in Macrophages In Vitro

Sildenafil (Viagra®) Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

Secreted frizzled‐related protein 5 protects against oxidative stress‐induced apoptosis in human aortic endothelial cells via downregulation of Bax

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