International Journal of Molecular Sciences

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Special Issue Editor

Prof. Massimiliano Ruscica

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Guest Editor

Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20122 Milan, Italy
Interests: atherosclerosis; metabolic disorders; cardiovascular disease

Special Issue Information

Dear Colleagues,

Atherosclerosis is a fibroproliferative disease that proceeds through a series of pathological events involving the inflammatory and immune systems as well as the different types of cells and matrix proteins of the vascular wall. The disease is accompanied by the subendothelial accumulation of lipids and fibrous connective tissue, the phenotypic modulation of SMCs, and the migration of a group of cells, notably monocytes and T cells, through the vascular endothelium in response to inflammation. In addition to well-known factors (e.g., high blood pressure, dyslipidemia, diabetes, excess body weight), there are several emerging factors associated with atherosclerosis such as inflammation, endothelial dysfunction, intestinal microbiota alteration, uric acid, vitamin D, or miRNA expression that could potentially explain the residual cardiovascular risk. Great progress has been made to increase our understanding of the molecular aspects that promote atherosclerosis initiation and progression, giving us the opportunity to develop new strategies for preventing and treating cardiovascular diseases.

This Special Issue of IJMS, ‘Atherosclerosis: From Molecular Basis to Therapy’, led by Prof. Massimiliano Ruscica, aims to focus on new insights, novel developments and discoveries, current challenges, and future perspectives in the field of atherosclerosis.

Prof. Massimiliano Ruscica
Guest Editor

Manuscript Submission Information

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Keywords

atherosclerosis
molecular basis
cardiovascular disease
artery disease
vascular dementia

Published Papers (2 papers)

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Research

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16 pages, 3961 KiB

Open AccessArticle

Gene Silencing of Angiopoietin-like 3 (ANGPTL3) Induced De Novo Lipogenesis and Lipid Accumulation in Huh7 Cell Line

by Ilaria Rossi, Giorgia Marodin, Maria Giovanna Lupo, Maria Pia Adorni, Bianca Papotti, Stefano Dall’Acqua and Nicola Ferri

Int. J. Mol. Sci. 2024, 25(7), 3708; https://doi.org/10.3390/ijms25073708 - 26 Mar 2024

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Abstract

Angiopoietin-like 3 (ANGPTL3) is a hepatokine acting as a negative regulator of lipoprotein lipase (LPL). Vupanorsen, an ANGPTL3 directed antisense oligonucleotide, showed an unexpected increase in liver fat content in humans. Here, we investigated the molecular mechanism linking ANGPTL3 silencing to hepatocyte fat accumulation. Human hepatocarcinoma Huh7 cells were treated with small interfering RNA (siRNA) directed to ANGPTL3, human recombinant ANGPTL3 (recANGPTL3), or their combination. Using Western blot, Oil Red-O, biochemical assays, and ELISA, we analyzed the expression of genes and proteins involved in lipid metabolism. Oil Red-O staining demonstrated that lipid content increased after 48 h of ANGPTL3 silencing (5.89 ± 0.33 fold), incubation with recANGPTL3 (4.08 ± 0.35 fold), or their combination (8.56 ± 0.18 fold), compared to untreated cells. This effect was also confirmed in Huh7-LX2 spheroids. A total of 48 h of ANGPTL3 silencing induced the expression of genes involved in the de novo lipogenesis, such as fatty acid synthase, stearoyl-CoA desaturase, ATP citrate lyase, and Acetyl-Coenzyme A Carboxylase 1 together with the proprotein convertase subtilisin/kexin 9 (PCSK9). Time-course experiments revealed that 6 h post transfection with ANGPTL3-siRNA, the cholesterol esterification by Acyl-coenzyme A cholesterol acyltransferase (ACAT) was reduced, as well as total cholesterol content, while an opposite effect was observed at 48 h. Under the same experimental conditions, no differences in secreted apoB and PCSK9 were observed. Since PCSK9 was altered by the treatment, we tested a possible co-regulation between the two genes. The effect of ANGPTL3-siRNA on the expression of genes involved in the de novo lipogenesis was not counteracted by gene silencing of PCSK9. In conclusion, our in vitro study suggests that ANGPTL3 silencing determines lipid accumulation in Huh7 cells by inducing the de novo lipogenesis independently from PCSK9. Full article

(This article belongs to the Special Issue Atherosclerosis: From Molecular Basis to Therapy)

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Review

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22 pages, 659 KiB

Open AccessReview

The Molecular Basis of the Augmented Cardiovascular Risk in Offspring of Mothers with Hypertensive Disorders of Pregnancy

by Asimenia Svigkou, Vasiliki Katsi, Vasilios G. Kordalis and Konstantinos Tsioufis

Int. J. Mol. Sci. 2024, 25(10), 5455; https://doi.org/10.3390/ijms25105455 - 17 May 2024

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Abstract

The review examines the impact of maternal preeclampsia (PE) on the cardiometabolic and cardiovascular health of offspring. PE, a hypertensive disorder of pregnancy, is responsible for 2 to 8% of pregnancy-related complications. It significantly contributes to adverse outcomes for their infants, affecting the time of birth, the birth weight, and cardiometabolic risk factors such as blood pressure, body mass index (BMI), abdominal obesity, lipid profiles, glucose, and insulin. Exposure to PE in utero predisposes offspring to an increased risk of cardiometabolic diseases (CMD) and cardiovascular diseases (CVD) through mechanisms that are not fully understood. The incidence of CMD and CVD is constantly increasing, whereas CVD is the main cause of morbidity and mortality globally. A complex interplay of genes, environment, and developmental programming is a plausible explanation for the development of endothelial dysfunction, which leads to atherosclerosis and CVD. The underlying molecular mechanisms are angiogenic imbalance, inflammation, alterations in the renin–angiotensin–aldosterone system (RAAS), endothelium-derived components, serotonin dysregulation, oxidative stress, and activation of both the hypothalamic–pituitary–adrenal axis and hypothalamic–pituitary–gonadal axis. Moreover, the potential role of epigenetic factors, such as DNA methylation and microRNAs as mediators of these effects is emphasized, suggesting avenues for future research and therapeutic interventions. Full article

(This article belongs to the Special Issue Atherosclerosis: From Molecular Basis to Therapy)

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