Impact of Oxysterols on Cell Death, Proliferation, and Differentiation Induction: Current Status

Freitas, Fábio Alessandro de; Levy, Débora; Zarrouk, Amira; Lizard, Gérard; Bydlowski, Sérgio Paulo

doi:10.3390/cells10092301

Cited by 46 publications

(42 citation statements)

References 127 publications

(219 reference statements)

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“…The endothelial LDL is then oxidised to produce oxLDL [ 30 ]. This oxLDL, typified by oxysterols such as 7β-hydroxycholesterol and 27-hydroxycholesterol [ 31 ], is phagocytosed by macrophages, which thereby accumulate large amounts of cholesterol and become foam cells. If left unchecked, foam cells continue to accumulate, forming fatty striations in affected arterial walls that eventually lead to atherosclerosis.…”

Section: The Development Of An Atherosclerotic Plaque—a Closer Look A...mentioning

confidence: 99%

Chitosan Nanoparticles in Atherosclerosis—Development to Preclinical Testing

Sriamornsak

Dass

2022

Pharmaceutics

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Chitosan is a natural biopolymer that is present in an abundant supply in sources such as crustacean shells, mushrooms, and insect exoskeletons. It can be used to make a variety of types of drug formulations and is generally safe to use in vivo; plus, it has inherent cholesterol-reducing properties. While an abundance of papers has tested this biopolymer in nanoparticles in cancer and diabetes research, there is a lag of usage, and hence the paucity of information, in the area of cardiovascular research, specifically in atherosclerosis, the topic of this review. This review highlights some of the deficiencies in this niche area of research, examines the range of chitosan nanoparticles that have been researched to date, and proposes several ways forward to advance this field. Nanoparticles used for both diagnostic and therapeutic purposes are reviewed, with a discussion on how these nanoparticles could be better researched in future and what lays ahead as the field potentially moves towards clinical trials in future.

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Section: The Development Of An Atherosclerotic Plaque—a Closer Look A...mentioning

confidence: 99%

Chitosan Nanoparticles in Atherosclerosis—Development to Preclinical Testing

Sriamornsak

Dass

2022

Pharmaceutics

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“…Ample evidence depicted that MSCs delivery may benefit post-MI cardiac function (Davidson et al, 2021 ; Yan et al, 2020 ; Li et al, 2010 ). Up-to-date, a number of scenarios have been put forward for MSCs-offered cardioprotection including anti-apoptosis and pro-angiogenesis (de Freitas et al, 2021 ). More recently, autophagy was shown to positively correlate with metformin-induced heart regeneration in zebrafish and suggests the value of this diabetic drug for amelioration of MI injury (Xie et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Beclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarction

et al. 2022

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Mesenchymal stem cells (MSCs)-based therapy has displayed some promises in ischemia heart diseases although its efficacy may be affected by changes in surrounding environments. This study evaluated the role of autophagy insufficiency using Beclin1 haploinsufficiency (BECN+/−) on intra-myocardial MSC transplantation-evoked effect against myocardial infarction. Donor MSCs from C57BL/6 mice were labelled with cell-tracker CM Dil and were delivered into LV free wall adjacent to infarct region in wild-type (WT) and BECN+/− recipient mice following ligation of left main coronary artery (MI-MSCs). Ten days following MI, myocardial function was assessed using echocardiography. Cardiomyocyte contractility and intracellular Ca2+ were monitored using cardiomyocytes from the area-at-risk adjacent to infarct. CM-Dil labeled cells were tracked in MSCs recipient mice using fluorescence microscopy. Lectin, Masson trichrome staining and Western blot analysis were employed to determine cardiomyocyte area, scar fibrosis, apoptosis and inflammation. MI insult triggered scar fibrosis, LV chamber dilation, decreased fractional shortening, ejection fraction, cardiomyocyte shortening, maximal velocity of shortening and relengthening as well as prolonged relengthening, which were abrogated or attenuated by MSCs therapy in WT but not BECN+/− mice. MI decreased intracellular Ca2+ rise and decay in response to electrical stimuli without affecting resting intracellular Ca2+, which were reconciled by MSCs in WT but not BECN+/− mice. MSCs further attenuated MI-induced mitochondrial ultrastructural injury, apoptosis, inflammation and autophagy defects in peri-infarct area in WT but not BECN+/− mice. Collectively, our results suggested that autophagy insufficiency dampened in MSCs-elicited cardioprotection associated with dampened apoptosis and inflammation.

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“…Free radical derived 7-oxycholesterols [7β hydroxy cholesterol (7β-OHC) and 7-keto cholesterol (7-KC)] have been found in brain, CSF [ 14 ], and plasma from AD patients [ 15 ]. Since oxysterols are important mediators in variety of cell functions including intracellular signaling [ 4 ], cell death [ 16 ], cell-cell communications [ 17 ], and inflammation [ 15 ], alteration to oxysterol homeostasis affects cellular health.…”

Section: Introductionmentioning

confidence: 99%

Oxysterols and Oxysterol Sulfates in Alzheimer’s Disease Brain and Cerebrospinal Fluid

Dias

Shokr

Shephard

et al. 2022

JAD

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Background: Brain cholesterol levels are tightly regulated but increasing evidence indicates that cholesterol metabolism may drive Alzheimer’s disease (AD)-associated pathological changes. Recent advances in understanding of mitochondrial dysfunction in AD brain have presented a vital role played by mitochondria in oxysterol biosynthesis and their involvement in pathophysiology. Oxysterol accumulation in brain is controlled by various enzymatic pathways including sulfation. While research into oxysterol is under the areas of active investigation, there is less evidence for oxysterol sulfates levels in human brain. Objective: This study investigates the hypothesis that AD brain oxysterols detoxification via sulfation is impaired in later stages of disease resulting in oxysterol accumulation. Methods: Lipids were extracted from postmortem frozen brain tissue and cerebrospinal (CSF) from late- (Braak stage III-IV) and early- (Braak stage I-II) stage AD patients. Samples were spiked with internal standards prior to lipid extraction. Oxysterols were enriched with a two-step solid phase extraction using a polymeric SPE column and further separation was achieved by LC-MS/MS. Results: Oxysterols, 26-hydroxycholesterol (26-OHC), 25-hydroxycholesterol (25-OHC), and 7-oxycholesterol levels were higher in brain tissue and mitochondria extracted from late-stage AD brain tissue except for 24S-hydroxycholesterol, which was decreased in late AD. However, oxysterol sulfates are significantly lower in the AD frontal cortex. Oxysterols, 25-OHC, and 7-oxocholesterol was higher is CSF but 26-OHC and oxysterol sulfate levels were not changed. Conclusion: Our results show oxysterol metabolism is altered in AD brain mitochondria, favoring synthesis of 26-OHC, 25-OHC, and 7-oxocholesterol, and this may influence brain mitochondrial function and acceleration of the disease.

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Impact of Oxysterols on Cell Death, Proliferation, and Differentiation Induction: Current Status

Cited by 46 publications

References 127 publications

Chitosan Nanoparticles in Atherosclerosis—Development to Preclinical Testing

Chitosan Nanoparticles in Atherosclerosis—Development to Preclinical Testing

Beclin1 haploinsufficiency compromises mesenchymal stem cell-offered cardioprotection against myocardial infarction

Oxysterols and Oxysterol Sulfates in Alzheimer’s Disease Brain and Cerebrospinal Fluid

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