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Molecular Insights into Cholesterol Metabolism

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (20 May 2025) | Viewed by 1760

Special Issue Editor


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Guest Editor
Department of Clinical Medicine, University of São Paulo, São Paulo 05508-090, SP, Brazil
Interests: cholesterol metabolism regulation

Special Issue Information

Dear Colleagues,

This Special Issue presents molecular insights into cholesterol metabolism. In 1985, M. S. Brown and J. L. Goldstein were awarded the Novel Prize for their pioneering work that unraveled the cell molecular control of the cholesterol metabolism. Since then, although remarkable progress in the field has been observed, questions about cholesterol metabolism and its consequences for human atherosclerosis remain; these are detailed in this symposium.

Various drugs have been suggested to reduce the plasma concentration of cholesteryl ester transfer protein (CETP), but have been abandoned due to undesirable side effects. Nevertheless, some researchers continue to advocate their use in preventing atherosclerotic vascular disease. This controversy is explored in this symposium.

It has been known for decades that the human intestine has no fixed limit to its ability to absorb dietary cholesterol. However, it is not known whether the efficiency of intestinal absorption is regulated by genetic-dependent mechanisms in genetic hypercholesterolemias.

It is known that reverse cholesterol transport participates in the elimination of cholesterol from the human intestine, but it is not known whether certain pathologies that interfere with cholesterol metabolism, notably diabetes mellitus, disrupt this transport; this subject should therefore be studied.

Other proteins, such as those that transfer cholesterol and phospholipids between plasma proteins and between these and cells, are not known to be effectively involved in atherosclerosis; this is the case with phospholipid transfer protein (PLTP) and, notably, lecithin-cholesterol acyl transferase (LCAT), which is modified by well-established genetic causes that have been explored more extensively.

More recently, there has been research linking intestinal flora to the cholesterol metabolism, which leads us to assume that there may be a connection between these factors; there is therefore a need to explore whether the intestinal flora may have an unfavorable influence on cholesterol metabolism.

The treatment of hypercholesterolemia with a vast arsenal of cholesterol-lowering drugs is effective in protecting against atherosclerotic cardiovascular disease; meanwhile, animals with cholesterolemia characterized by low apoB-containing particles and increased apoA-containing particles are genetically protected against atherosclerosis. This leads to ask how drastic a reduction in apoB and an increase in apoA should be attained to achieve more effective protection against atherosclerosis. Linked to this question, it is essential to discuss the role of marine and plant-based n-3 PUFA in atherosclerotic cardiovascular disease. This area of research includes the efficacy versus the inconvenience of dietary supplementation with phytosterols and phytostanols.

Underlying this problem is also the question of whether plasma non-cholesterol sterols are reliable markers of cholesterol synthesis and intestinal absorption; this would allow genetic alterations to be identified and therefore treated and prevented.

Prof. Dr. Eder Rocha Quintão
Guest Editor

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Keywords

  • cholesterol metabolism
  • CETP
  • PLTP
  • LCAT
  • sitosterol
  • sitostanol
  • plant sterols
  • LDL
  • HDL
  • reverse cholesterol transport
  • non-cholesterol sterols
  • atherosclerosis

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Published Papers (1 paper)

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Research

13 pages, 1952 KiB  
Article
7-Ketocholesterol Effects on Osteogenic Differentiation of Adipose Tissue-Derived Mesenchymal Stem Cells
by Beatriz Araújo Oliveira, Débora Levy, Jessica Liliane Paz, Fabio Alessandro de Freitas, Cadiele Oliana Reichert, Alessandro Rodrigues and Sérgio Paulo Bydlowski
Int. J. Mol. Sci. 2024, 25(21), 11380; https://doi.org/10.3390/ijms252111380 - 23 Oct 2024
Cited by 2 | Viewed by 1372
Abstract
Some oxysterols were shown to promote osteogenic differentiation of mesenchymal stem cells (MSCs). Little is known about the effects of 7-ketocholesterol (7-KC) in this process. We describe its impact on human adipose tissue-derived MSC (ATMSC) osteogenic differentiation. ATMSCs were incubated with 7-KC in [...] Read more.
Some oxysterols were shown to promote osteogenic differentiation of mesenchymal stem cells (MSCs). Little is known about the effects of 7-ketocholesterol (7-KC) in this process. We describe its impact on human adipose tissue-derived MSC (ATMSC) osteogenic differentiation. ATMSCs were incubated with 7-KC in osteogenic or adipogenic media. Osteogenic and adipogenic differentiation was evaluated by Alizarin red and Oil Red O staining, respectively. Osteogenic (ALPL, RUNX2, BGLAP) and adipogenic markers (PPARƔ, C/EBPα) were determined by RT-PCR. Differentiation signaling pathways (SHh, Smo, Gli-3, β-catenin) were determined by indirect immunofluorescence. ATMSCs treated with 7-KC in osteogenic media stained positively for Alizarin Red. 7-KC in adipogenic media decreased the number of adipocytes. 7-KC increased ALPL and RUNX2 but not BGLAP expressions. 7-KC decreased expression of PPARƔ and C/EBPα, did not change SHh, Smo, and Gli-3 expression, and increased the expression of β-catenin. In conclusion, 7-KC favors osteogenic differentiation of ATMSCs through the expression of early osteogenic genes (matrix maturation phase) by activating the Wnt/β-catenin signaling pathway, while inhibiting adipogenic differentiation. This knowledge can be potentially useful in regenerative medicine, in treatments for bone diseases. Full article
(This article belongs to the Special Issue Molecular Insights into Cholesterol Metabolism)
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