Molecular and Cellular Mechanism of Atherosclerosis and Atherosclerotic Diseases: Focus on Lipid Accumulation and Inflammation

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 12503

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Petrovsky National Research Centre of Surgery, 2, Abrikosovsky Lane, 119991 Moscow, Russia
Interests: atherosclerosis; inflammation; macrophages; CRISPR/Cas9; low-density lipoprotein
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Dear Colleagues,

Atherosclerosis underlies many cardiovascular diseases, which are one of the leading causes of morbidity and mortality in the world. In atherosclerosis, chronic inflammation and lipid deposition in the intima of large vessels develop, ultimately leading to the formation of lipo-fibrotic lesions. Genetic and epigenetic factors are the focus of attention of researchers involved in the prevention and treatment of atherosclerosis. Epidemiological studies assert that these factors can explain some variability of atherosclerotic diseases. All kinds of cellular and murine models of atherosclerosis, which allow studying molecular and cellular processes of atherogenesis, including signaling pathways, are being created. Nevertheless, there is still debate about what is the main cause of atherosclerosis: accumulation of lipids or chronic inflammation in the vascular wall. In recent years, researchers have begun to assign a leading role in the progression of this disease to inflammation. Inflammation can alter the functionality of cells, facilitating foam cell formation and apoptosis. Despite this, in the classical view, modified LDL induces the accumulation of intracellular cholesterol, which in turn leads to a cellular pro-inflammatory response. However, in the light of inflammatory theory, the reverse process is most likely possible: pro-inflammatory cytokines are triggers that promote the accumulation of cholesterol in the cell, including when interacting with modified LDL. Future research will be able to solve this problem.

We kindly welcome original research papers or reviews to contribute to this Special Issue of Life.

Dr. Vasily Sukhorukov
Guest Editor

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Keywords

  • atherosclerosis
  • lipid metabolism
  • inflammation
  • macrophages
  • genetic and epigenetic factors

Published Papers (4 papers)

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Research

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13 pages, 1615 KiB  
Article
Low Levels of Serum Fetuin-A and Retinol-Binding Protein 4 Correlate with Lipoprotein Subfractions in Morbid Obese and Lean Non-Diabetic Subjects
by Hajnalka Lőrincz, Imre Csige, Mariann Harangi, Anita Szentpéteri, Ildikó Seres, Zoltán Szabó, György Paragh and Sándor Somodi
Life 2021, 11(9), 881; https://doi.org/10.3390/life11090881 - 27 Aug 2021
Cited by 4 | Viewed by 1863
Abstract
Background: Fetuin-A and retinol-binding protein 4 (RBP4) are secreted as both hepatokine and adipokine. These are involved in insulin resistance, obesity-related dyslipidemia, and atherosclerosis. To date, correlations of circulating fetuin-A and RBP4 with lipoprotein subfractions as well as high-density lipoprotein (HDL)-linked proteins have [...] Read more.
Background: Fetuin-A and retinol-binding protein 4 (RBP4) are secreted as both hepatokine and adipokine. These are involved in insulin resistance, obesity-related dyslipidemia, and atherosclerosis. To date, correlations of circulating fetuin-A and RBP4 with lipoprotein subfractions as well as high-density lipoprotein (HDL)-linked proteins have not been entirely investigated in morbid obese and lean non-diabetic subjects. Methods: One-hundred obese non-diabetic patients (body mass index, BMI: 42.5 ± 8.1 kg/m2) along with 32 gender and age-matched normal weight controls (BMI: 24.5 ± 2.5 kg/m2) were enrolled in our study. Serum fetuin-A and RBP4 were measured by ELISA. Lipoprotein subfractions were distributed by Lipoprint gelelectrophoresis. Results: Serum fetuin-A and RBP4 were unexpectedly lower in obese patients (p < 0.01 and p < 0.01, respectively) compared to controls and correlated with each other (r = 0.37; p < 0.001). Fetuin-A had positive correlations with HDL-C (r = 0.22; p = 0.02), apolipoprotein AI (apoAI) (r = 0.33; p < 0.001), very-low density lipoprotein (VLDL) subfraction (r = 0.18; p = 0.05), and large HDL subfraction levels (r = 0.3; p = 0.001) but did not show correlation with carbohydrate parameters in all subjects. RBP4 correlated positively with HDL-C (r = 0.2; p = 0.025), apoAI (r = 0.23; p = 0.01), VLDL subfraction (r = 0.37; p < 0.001), intermediate HDL subfraction (r = 0.23; p = 0.01), and small HDL subfraction (r = 0.21; p = 0.02) concentrations, as well as C-peptide levels in overall participants. Backward stepwise multiple regression analysis showed that serum fetuin-A concentration is best predicted by RBP4 and large HDL subfraction. In model 2, VLDL subfraction was the independent predictor of serum RBP4 level. Conclusions: Our data may indicate a potential role of fetuin-A and RBP4 in impaired lipoprotein metabolism associated with obesity. Full article
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12 pages, 1867 KiB  
Article
Prediction of Insulin Resistance by Modified Triglyceride Glucose Indices in Youth
by Kyungchul Song, Goeun Park, Hye Sun Lee, Youngha Choi, Jun Suk Oh, Han Saem Choi, Junghwan Suh, Ahreum Kwon, Ho-Seong Kim and Hyun Wook Chae
Life 2021, 11(4), 286; https://doi.org/10.3390/life11040286 - 28 Mar 2021
Cited by 19 | Viewed by 2941
Abstract
The triglyceride glucose (TyG) index, derived from a combination of fasting glucose and triglycerides, has been suggested as a useful marker for insulin resistance (IR), in addition to modified TyG indices that combine obesity parameters. This study investigated the association and utility of [...] Read more.
The triglyceride glucose (TyG) index, derived from a combination of fasting glucose and triglycerides, has been suggested as a useful marker for insulin resistance (IR), in addition to modified TyG indices that combine obesity parameters. This study investigated the association and utility of TyG and modified TyG indices for IR prediction in youth. Based on the Korea National Health and Nutritional Examination Survey, the data of 3728 youth aged 10–19 years were analyzed. Odds ratios (ORs) and 95% confidence intervals (CIs) of tertiles 2 and 3 for each parameter were calculated and compared with tertile 1 as a reference. To compare the parameters for identifying IR, receiver operating characteristic curves were plotted and the area under the curve (AUC) was calculated. The ORs and 95% CIs for insulin resistance (IR) progressively increased across tertiles of each parameter. Overall, all modified TyG indices presented higher ORs and AUC than the TyG index. The TyG-body mass index standard deviation score showed the largest AUC for IR detection in all subjects. In conclusion, TyG and modified TyG indices could be used as valuable markers for the prediction of IR in youth. Moreover, modified TyG indices had better diagnostic accuracy than the TyG index. Full article
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20 pages, 2584 KiB  
Article
Atheroprotective Properties of Costus spicatus (Jacq.) Sw. in Female Rats
by Bethânia Rosa Lorençone, Lucas Pires Guarnier, Rhanany Alan Calloi Palozi, Paulo Vitor Moreira Romão, Aline Aparecida Macedo Marques, Lislaine Maria Klider, Roosevelt Isaias Carvalho Souza, Ariany Carvalho dos Santos, Cleide Adriane Signor Tirloni, Nadla Soares Cassemiro, Denise Brentan Silva, Jane Manfron Budel and Arquimedes Gasparotto Junior
Life 2021, 11(3), 212; https://doi.org/10.3390/life11030212 - 8 Mar 2021
Cited by 4 | Viewed by 2585
Abstract
Background: Costus spicatus (Jacq.) Sw. is a medicinal species frequently prescribed for the treatment of cardiovascular diseases. This study aims to evaluate the effects of this species against the development of atherosclerosis. Methods: First, an anatomical study of the C. spicatus leaves was [...] Read more.
Background: Costus spicatus (Jacq.) Sw. is a medicinal species frequently prescribed for the treatment of cardiovascular diseases. This study aims to evaluate the effects of this species against the development of atherosclerosis. Methods: First, an anatomical study of the C. spicatus leaves was performed. Then, the extract (ESCS) was obtained and submitted to phytochemical analysis. Female rats were treated with a single dose of ESCS (2000 mg/kg) to assess acute toxicity. Other groups of female rats received an atherogenic diet for 60 days. After 30 days, the animals were treated orally with ESCS (30 and 300 mg/kg), rosuvastatin (5 mg/kg), or vehicle once daily for 30 days. Serum lipids oxidized low-density lipoprotein, soluble adhesion molecules, interleukins 1β and 6, and markers of renal and liver function were measured. Renal function, blood pressure, electrocardiography, and vascular reactivity were also evaluated. Arteries, heart, liver, and kidney were also collected to evaluate the tissue redox state and histopathological analysis. Results: Prolonged treatment with ESCS induces significant hypolipidemic and antioxidant effects, that prevent endothelial dysfunction and modulated the local inflammatory process, reducing the evolution of the atherosclerotic disease. Conclusions: This study provides a scientific basis for the popular use of C. spicatus for the treatment of atherosclerosis. Full article
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Review

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14 pages, 650 KiB  
Review
Molecular Pathogenesis and the Possible Role of Mitochondrial Heteroplasmy in Thoracic Aortic Aneurysm
by A. V. Suslov, M. A. Afanasyev, P. A. Degtyarev, P. V. Chumachenko, M. Bagheri Ekta, V. N. Sukhorukov, V. A. Khotina, S.-F. Yet, I. A. Sobenin and A. Yu Postnov
Life 2021, 11(12), 1395; https://doi.org/10.3390/life11121395 - 13 Dec 2021
Cited by 2 | Viewed by 3804
Abstract
Thoracic aortic aneurysm (TAA) is a life-threatening condition associated with high mortality, in which the aortic wall is deformed due to congenital or age-associated pathological changes. The mechanisms of TAA development remain to be studied in detail, and are the subject of active [...] Read more.
Thoracic aortic aneurysm (TAA) is a life-threatening condition associated with high mortality, in which the aortic wall is deformed due to congenital or age-associated pathological changes. The mechanisms of TAA development remain to be studied in detail, and are the subject of active research. In this review, we describe the morphological changes of the aortic wall in TAA. We outline the genetic disorders associated with aortic enlargement and discuss the potential role of mitochondrial pathology, in particular mitochondrial DNA heteroplasmy, in the disease pathogenesis. Full article
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