The role of Fenton reaction in ROS-induced toxicity underlying atherosclerosis – modeled and analyzed using a Petri net-based approach

Formanowicz, Dorota; Radom, Marcin; Rybarczyk, Agnieszka; Formanowicz, Piotr

doi:10.1016/j.biosystems.2018.01.002

Cited by 32 publications

(22 citation statements)

References 46 publications

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“…NO acts as an important antioxidant agent against Fenton’s reaction which generates highly reactive hydroxyl radicals 85 86. Hydroxyl radicals can lead to many disturbances which contribute to the endothelial dysfunction and act as a starting point for atherosclerosis 87. Dyslipidaemia is closely associated with the progression of coronary atherosclerosis, and it accounts for around 50% of the population-attributable risk of CAD 88.…”

Section: Discussionmentioning

confidence: 99%

Associations of theNOS3rs1799983 polymorphism with circulating nitric oxide and lipid levels: a systematic review and meta-analysis

Wang

Jia

et al. 2019

Postgraduate Medical Journal

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BackgroundCirculating nitric oxide (NO) and lipid levels are closely associated with coronary artery disease (CAD). It is unclear whether the rs1799983 polymorphism in endothelial nitric oxide synthase (NOS3) gene is associated with plasma levels of NO and lipids. This systematic review and meta-analysis (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) aimed to clarify the relationships between the rs1799983 polymorphism and plasma levels of NO and lipids.MethodsSixteen studies (2702 subjects) and 59 studies (14 148 subjects) were identified for the association analyses for NO and lipids, respectively. Mean difference (MD) and 95% CI were used to estimate the effects of the rs1799983 polymorphism on plasma NO and lipid levels. The primary outcome variable was NO, and the secondary outcomes included triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C).ResultsCarriers of the T allele had lower levels of NO (MD −0.27 μmol/L, 95% CI −0.42 to −0.12 μmol/L, p<0.001) and HDL-C (MD −0.07 mmol/L, 95% CI −0.14 to −0.00 mmol/L, p=0.04), and higher levels of TC (MD 0.13 mmol/L, 95% CI 0.06 to 0.20 mmol/L, p<0.001) and LDL-C (MD 0.14 mmol/L, 95% CI 0.05 to 0.22 mmol/L, p=0.002) than the non-carriers. Triglyceride levels were comparable between the genotypes.ConclusionThe association between the NOS3 rs1799983 polymorphism and CAD may be partly mediated by abnormal NO and lipid levels caused by the T allele.

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Section: Discussionmentioning

confidence: 99%

Associations of theNOS3rs1799983 polymorphism with circulating nitric oxide and lipid levels: a systematic review and meta-analysis

Wang

Jia

et al. 2019

Postgraduate Medical Journal

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“…Such an analysis allows for answering the question: which subprocesses will be excluded from the modeled system, if, for some reasons, the selected transition (some reaction) will be deactivated. Selected articles that used knockout analysis are [ 17 , 18 ]. The knockout analysis concerned two different types of macrophages: M1 and M2.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, looking for subsets of elementary processes which are common for some higher level subprocesses can lead to discoveries of some properties of the system. It can be done by looking for similarities between t-invariants (which is equivalent to a similarity between their supports if a proper similarity measure is used) [ 17 , 74 ].…”

Section: Methodsmentioning

confidence: 99%

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Theoretical Studies on the Engagement of Interleukin 18 in the Immuno-Inflammatory Processes Underlying Atherosclerosis

Formanowicz

Gutowska

Formanowicz

2018

IJMS

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Interleukin 18 (IL-18) is one of the pro-inflammatory cytokines expressed by macrophages, suggesting that it plays important physiological and immunological functions, among the others: stimulation of natural killers (NKs) and T cells to interferon gamma (IFN-γ) synthesis. IL-18 was originally identified as interferon gamma inducing factor and now it is recognized as multifunctional cytokine, which has a role in regulation of innate and adaptive immune responses. Therefore, in order to investigate IL-18 contribution to the immuno-inflammatory processes underlying atherosclerosis, a systems approach has been used in our studies. For this purpose, a model of the studied phenomenon, including selected pathways, based on the Petri-net theory, has been created and then analyzed. Two pathways of IL-18 synthesis have been distinguished: caspase 1-dependent pathway and caspase 1-independent pathway. The analysis based on t-invariants allowed for determining interesting dependencies between IL-18 and different types of macrophages: M1 are involved in positive regulation of IL-18, while M2 are involved in negative regulation of IL-18. Moreover, the obtained results showed that IL-18 is produced more often via caspase 1-independent pathway than caspase 1-dependent pathway. Furthermore, we found that this last pathway may be associated with caspase 8 action.

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“…The local plaque environment favors hemolysis of RBC, releasing heme and iron in the intimal lesions. Recent systems biology analyses point to hydroxyl radical derived through Fenton chemistry as an agonist in atherogenesis (6) . In addition, genome-wide association studies have implicated iron metabolism and hepcidin as risk factors for biomarkers of atherosclerosis such as increased intima-media thickness (7) .…”

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confidence: 99%

Internal Bleeding

Michel

Libby

Franck

2018

JACC: Basic to Translational Science

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The role of Fenton reaction in ROS-induced toxicity underlying atherosclerosis – modeled and analyzed using a Petri net-based approach

Cited by 32 publications

References 46 publications

Associations of theNOS3rs1799983 polymorphism with circulating nitric oxide and lipid levels: a systematic review and meta-analysis

Associations of theNOS3rs1799983 polymorphism with circulating nitric oxide and lipid levels: a systematic review and meta-analysis

Theoretical Studies on the Engagement of Interleukin 18 in the Immuno-Inflammatory Processes Underlying Atherosclerosis

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