Immunopathology of Atherosclerosis and Related Diseases: Focus on Molecular Biology

Bezsonov, Evgeny E.; Sobenin, Igor A.; Orekhov, Alexander N.

doi:10.3390/ijms22084080

Cited by 27 publications

(24 citation statements)

References 30 publications

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“…A large number of studies have shown that the pathogenesis of AS includes hyperlipidemia, vascular endothelial dysfunction, inflammation and oxidative stress [ 4 , 5 , 6 ]. Besides, the increased immunogenicity of desialylated low-density lipoprotein (LDL) and mitochondrial mutations were also involved in the development of AS [ 7 , 8 ]. Among them, endothelial dysfunction and inflammation play pivotal roles in the initiation of AS.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Selenium Nanoparticles and Sodium Selenite on the Alleviation of Early Atherosclerosis by Inhibiting Endothelial Dysfunction and Inflammation in Apolipoprotein E-Deficient Mice

Xiao

et al. 2021

IJMS

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Atherosclerosis and related cardiovascular diseases represent the greatest threats to human health, worldwide. Previous animal studies showed that selenium nanoparticles (SeNPs) and Na2SeO3 might have anti-atherosclerotic activity, but the underlying mechanisms are poorly elucidated. This study compared the anti-atherosclerotic activity of SeNPs stabilized with chitosan (CS-SeNPs) and Na2SeO3 and the related mechanism in a high-fat-diet-fed apolipoprotein E-deficient mouse model of atherosclerosis. The results showed that oral administration of both CS-SeNPs and Na2SeO3 (40 μg Se/kg/day) for 10 weeks significantly reduced atherosclerotic lesions in mouse aortae. Mechanistically, CS-SeNPs and Na2SeO3 not only alleviated vascular endothelial dysfunction, as evidenced by the increase of serum nitric oxide level and the decrease of aortic adhesion molecule expression, but also vascular inflammation, as evidenced by the decrease of macrophage recruitment as well as the expression of proinflammatory molecules. Importantly, these results were replicated within in-vivo experiments on the cultured human endothelial cell line EA.hy926. Overall, CS-SeNPs had a comparable effect with Na2SeO3 but might have more potential in atherosclerosis prevention due to its lower toxicity. Together, these results provide more insights into the mechanisms of selenium against atherosclerosis and further highlight the potential of selenium supplementation as a therapeutic strategy for atherosclerosis.

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Section: Introductionmentioning

confidence: 99%

Comparison of Selenium Nanoparticles and Sodium Selenite on the Alleviation of Early Atherosclerosis by Inhibiting Endothelial Dysfunction and Inflammation in Apolipoprotein E-Deficient Mice

Xiao

et al. 2021

IJMS

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“…In normal cases, a tolerance develops, and the macrophage stops releasing cytokines. However, in the presence of mitochondrial mutations, tolerance formation may be impaired, which could lead to continuous secretion of inflammatory cytokines and chronic inflammation development [ 3 , 4 ].…”

Section: Figurementioning

confidence: 99%

“…One promising hypothesis combining different observations related to atherosclerosis pathology is that mutations of mitochondrial DNA could modulate the inflammatory response of macrophages to different pro-inflammatory stimuli, leading to chronic inflammation and further development of the disease [ 3 , 4 ]. As a part of the innate immune system, macrophages are capable of recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), and can trigger immune response.…”

mentioning

confidence: 99%

Macrophages in Health and Non-Infectious Disease 2.0

2022

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“…Accumulating evidence indicates that numerous miRNAs play a pivotal role in both atherosclerotic initiation and progression. miRNAs are highly conserved, single-stranded noncoding RNA molecules, exerting post-transcriptional effects on gene expression by promoting degradation of mRNA target and/or inhibiting mRNA translation [ 37 ]. Accordingly, they participate in positive as well as negative regulatory loops resulting in a hierarchical network.…”

Section: Alternative Hypotheses On Atherosclerotic Lesion Initiation and Progressionmentioning

confidence: 99%

The Initial Human Atherosclerotic Lesion and Lipoprotein Modification—A Deep Connection

Torzewski

2021

IJMS

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Atherosclerosis research typically focuses on the evolution of intermediate or advanced atherosclerotic lesions rather than on prelesional stages of atherogenesis. Yet these early events may provide decisive leads on the triggers of the pathologic process, before lesions become clinically overt. Thereby, it is mandatory to consider extracellular lipoprotein deposition at this stage as the prerequisite of foam cell formation leading to a remarkable accumulation of LDL (Low Density Lipoproteins). As progression of atherosclerosis displays the characteristic features of a chronic inflammatory process on the one hand and native LDL lacks inflammatory properties on the other hand, the lipoprotein must undergo biochemical modification to become atherogenic. During the last 25 years, evidence was accumulated in support of a different concept on atherogenesis proposing that modification of native LDL occurs through the action of ubiquitous hydrolytic enzymes (enzymatically modified LDL or eLDL) rather than oxidation and contending that the physiological events leading to macrophage uptake and reverse transport of eLDL first occur without inflammation (initiation with reversion). Preventing or reversing initial atherosclerotic lesions would avoid the later stages and therefore prevent clinical manifestations. This concept is in accordance with the response to retention hypothesis directly supporting the strategy of lowering plasma levels of atherogenic lipoproteins as the most successful therapy for atherosclerosis and its sequelae. Apart from but unquestionable closely related to this concept, there are several other hypotheses on atherosclerotic lesion initiation favoring an initiating role of the immune system (‘vascular-associated lymphoid tissue’ (VALT)), defining foam cell formation as a variant of lysosomal storage disease, relating to the concept of the inflammasome with crystalline cholesterol and/or mitochondrial DAMPs (damage-associated molecular patterns) being mandatory in driving arterial inflammation and, last but not least, pointing to miRNAs (micro RNAs) as pivotal players. However, direct anti-inflammatory therapies may prove successful as adjuvant components but will likely never be used in the absence of strategies to lower plasma levels of atherogenic lipoproteins, the key point of the perception that atherosclerosis is not simply an inevitable result of senescence. In particular, given the importance of chemical modifications for lipoprotein atherogenicity, regulation of the enzymes involved might be a tempting target for pharmacological research.

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Immunopathology of Atherosclerosis and Related Diseases: Focus on Molecular Biology

Abstract: In this Special Issue of the International Journal of Molecular Sciences, we include insightful reviews and research papers on the subject “Immunopathology of Atherosclerosis and Related Diseases: Focus on Molecular Biology”.[...]

Cited by 27 publications

References 30 publications

Comparison of Selenium Nanoparticles and Sodium Selenite on the Alleviation of Early Atherosclerosis by Inhibiting Endothelial Dysfunction and Inflammation in Apolipoprotein E-Deficient Mice

Comparison of Selenium Nanoparticles and Sodium Selenite on the Alleviation of Early Atherosclerosis by Inhibiting Endothelial Dysfunction and Inflammation in Apolipoprotein E-Deficient Mice

Macrophages in Health and Non-Infectious Disease 2.0

The Initial Human Atherosclerotic Lesion and Lipoprotein Modification—A Deep Connection

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