Introduction of the special issue “Atherosclerosis and Related Diseases”

Orekhov, Alexander N.; Ivanova, Ekaterina A.

doi:10.20517/2574-1209.2017.33

Cited by 20 publications

(17 citation statements)

References 7 publications

(8 reference statements)

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“…Despite the above limitations, the results of our study suggest that environmental and genetic factors are involved in the formation of susceptibility to atherosclerosis and should be considered as plausible risk factors for cardiovascular diseases. However, the question on the plausibility of findings in routine clinical practice and preventive medicine remains disputable [21] . It is likely that early awareness on individual genetic predisposition to atherosclerosis may be the motivating factor for higher personal compliance to healthy lifestyle in more beneficial ecologic environment.…”

Section: Discussionmentioning

confidence: 99%

Profiling of risk of subclinical atherosclerosis: possible interplay of genetic and environmental factors as the update of conventional approach

Sobenin¹,

Myasoedova²,

Kirichenko³

et al. 2019

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Aim:To explore whether geographical location, genetic and environmental factors are associated with carotid atherosclerosis in high-risk individuals. Methods:In Moscow 470 apparently healthy, asymptomatic volunteer subjects with a high cardiovascular disease risk were recruited to participate in a cross-sectional study. Carotid intima-media thickness (cIMT), a validated biomarker for present and future cardiovascular disease risk, was assessed by means of high resolution ultrasound scans in subjects. Results:The total burden of conventional cardiovascular risk factors explained 21% of the cIMT variability; the mutational burden of mitochondrial genome defined by heteroplasmic mutations m.652delG, m.3256C>T, m.13513G>A, m.14459G>A, and m.15059G>A independently explained 23% variability; the combination of conventional and genetic risk factors increased explanatory level to 36%. Further exploratory statistical analyses showed air pollution as an independent risk factor for cIMT. Conclusion:In our study we confirmed and expanded the existence of a European geographic gradient of atherosclerosis risk and its association with cardiovascular disease risk. Geographical, environmental (particularly, air pollution) -and genetic risk factors (particularly, mutant variants of mitochondrial genome) may interplay in the formation of susceptibility to atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Profiling of risk of subclinical atherosclerosis: possible interplay of genetic and environmental factors as the update of conventional approach

Sobenin¹,

Myasoedova²,

Kirichenko³

et al. 2019

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“…In addition to 5-ALA, there are many other mitochondria targeting substances. This is a good arsenal for a broad search for potential drugs for subcellular therapy including anti-atherosclerotic therapy [4,5] .…”

Section: Dear Editormentioning

confidence: 99%

Subcellular anti-atherosclerotic therapy

Ryabova¹,

Romanishkin²,

Skobeltsin³

et al. 2019

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“…Noteworthy, intracellular lipid accumulation is not associated with the high levels of total cholesterol but with the atherogenic LDL cholesterol. Several authors indicated that LDL particles become atherogenic, i.e., acquire the ability to cause intracellular lipid accumulation (atherogenicity) after their chemical modification, such as desialylation, oxidation, acetylation, and others [3][4][5][6]. Meanwhile, the attempts of inducing lipid accumulation in cultured cells by incubation with native LDL were not successful.…”

Section: Introductionmentioning

confidence: 99%

Role of Phagocytosis in the Pro-Inflammatory Response in LDL-Induced Foam Cell Formation; a Transcriptome Analysis

Orekhov

Nikiforov

Sukhorukov

et al. 2020

IJMS

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Excessive accumulation of lipid inclusions in the arterial wall cells (foam cell formation) caused by modified low-density lipoprotein (LDL) is the earliest and most noticeable manifestation of atherosclerosis. The mechanisms of foam cell formation are not fully understood and can involve altered lipid uptake, impaired lipid metabolism, or both. Recently, we have identified the top 10 master regulators that were involved in the accumulation of cholesterol in cultured macrophages induced by the incubation with modified LDL. It was found that most of the identified master regulators were related to the regulation of the inflammatory immune response, but not to lipid metabolism. A possible explanation for this unexpected result is a stimulation of the phagocytic activity of macrophages by modified LDL particle associates that have a relatively large size. In the current study, we investigated gene regulation in macrophages using transcriptome analysis to test the hypothesis that the primary event occurring upon the interaction of modified LDL and macrophages is the stimulation of phagocytosis, which subsequently triggers the pro-inflammatory immune response. We identified genes that were up- or downregulated following the exposure of cultured cells to modified LDL or latex beads (inert phagocytosis stimulators). Most of the identified master regulators were involved in the innate immune response, and some of them were encoding major pro-inflammatory proteins. The obtained results indicated that pro-inflammatory response to phagocytosis stimulation precedes the accumulation of intracellular lipids and possibly contributes to the formation of foam cells. In this way, the currently recognized hypothesis that the accumulation of lipids triggers the pro-inflammatory response was not confirmed. Comparative analysis of master regulators revealed similarities in the genetic regulation of the interaction of macrophages with naturally occurring LDL and desialylated LDL. Oxidized and desialylated LDL affected a different spectrum of genes than naturally occurring LDL. These observations suggest that desialylation is the most important modification of LDL occurring in vivo. Thus, modified LDL caused the gene regulation characteristic of the stimulation of phagocytosis. Additionally, the knock-down effect of five master regulators, such as IL15, EIF2AK3, F2RL1, TSPYL2, and ANXA1, on intracellular lipid accumulation was tested. We knocked down these genes in primary macrophages derived from human monocytes. The addition of atherogenic naturally occurring LDL caused a significant accumulation of cholesterol in the control cells. The knock-down of the EIF2AK3 and IL15 genes completely prevented cholesterol accumulation in cultured macrophages. The knock-down of the ANXA1 gene caused a further decrease in cholesterol content in cultured macrophages. At the same time, knock-down of F2RL1 and TSPYL2 did not cause an effect. The results obtained allowed us to explain in which way the inflammatory response and the accumulation of cholesterol are related confirming our hypothesis of atherogenesis development based on the following viewpoints: LDL particles undergo atherogenic modifications that, in turn, accompanied by the formation of self-associates; large LDL associates stimulate phagocytosis; as a result of phagocytosis stimulation, pro-inflammatory molecules are secreted; these molecules cause or at least contribute to the accumulation of intracellular cholesterol. Therefore, it became obvious that the primary event in this sequence is not the accumulation of cholesterol but an inflammatory response.

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Introduction of the special issue “Atherosclerosis and Related Diseases”

Cited by 20 publications

References 7 publications

Profiling of risk of subclinical atherosclerosis: possible interplay of genetic and environmental factors as the update of conventional approach

Profiling of risk of subclinical atherosclerosis: possible interplay of genetic and environmental factors as the update of conventional approach

Subcellular anti-atherosclerotic therapy

Role of Phagocytosis in the Pro-Inflammatory Response in LDL-Induced Foam Cell Formation; a Transcriptome Analysis

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