Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation?

Rádiková, Žofia; Penesová, Adela; Havranová, Andrea; Sivakova, Monika; Šiarnik, Pavel; Žitňanová, Ingrid; Imrich, Richard; Turčãni, Peter; Kollár, Branislav

doi:10.1186/s12944-020-01221-x

Cited by 16 publications

(16 citation statements)

References 47 publications

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“…Reports related to FNG, NTZ, and IFN β-1a had mostly ADRs involving metabolic disorders, especially dyslipidemia, even if a retrospective observational study suggests that routine lipid profile monitoring is unnecessary during FNG treatment in MS patients without pre-existing cardiovascular comorbidities ( Rauma et al, 2020 ). A recent study has shown the correlation between MS-related systemic inflammation and the onset of mild dyslipidemia, especially in males in the early stages of the disease ( Rádiková et al, 2020 ). Moreover, dyslipidemia can influence, as a cardiovascular risk factor, the course of the disease, leading to a greater risk of progression to disability ( Kowalec et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Adverse Drug Reactions with Drugs Used in Multiple Sclerosis: An Analysis from the Italian Pharmacovigilance Database

et al. 2022

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Given the importance of inflammation at the onset of multiple sclerosis (MS), therapy is mainly based on the use of anti-inflammatory drugs including disease modifying therapies (DMTs). Considering the recent approval of some DMTs, pharmacovigilance becomes a fundamental tool for the acquisition of new safety data. The aim of the study was to analyze adverse drug reactions (ADRs) related to the use of drugs approved for MS. All national publicly-available aggregated ADR reports recorded from 2002 to 2020 into the Reports of Adverse Reactions of Medicines (RAM) system and all complete Sicilian data reported into the Italian spontaneous reporting system (SRS) database having as suspected drugs interferon β-1a (IFN β-1a), interferon β-1b (IFN β-1b), peginterferon β-1a (PEG-IFN β-1a), glatiramer acetate (GA), natalizumab (NTZ), fingolimod (FNG), teriflunomide (TRF), dimethyl fumarate (DMF), alemtuzumab (Alem), ocrelizumab (OCZ), or cladribine (Cladr), were collected. Descriptive analyses of national, publicly-available aggregated data and full-access regional data were performed to assess demographic characteristics and drug-related variables followed by a more in-depth analysis of all Sicilian ADRs with a case-by-case assessment and a disproportionality analysis of unexpected ADRs. A total of 13,880 national reports have been collected from 2002 to 2020: they were mainly not serious ADRs (67.9% vs. 26.1%) and related to females (71.7% vs. 26.3%) in the age group 18–65 years (76.5%). The most reported ADRs were general and administration site conditions (n = 6,565; 47.3%), followed by nervous (n = 3,090; 22.3%), skin (n = 2,763; 19.9%) and blood disorders (n = 2,180; 15.7%). Some unexpected Sicilian ADRs were shown, including dyslipidemia for FNG (n = 10; ROR 28.5, CI 14.3–59.6), NTZ (n = 5; 10.3, 4.1–25.8), and IFN β-1a (n = 4; 8.7, 3.1–24.1), abortion and alopecia for NTZ (n = 9; 208.1, 73.4–590.1; n = 3; 4.9, 1.5–15.7), and vitamin D deficiency for GA (n = 3; 121.2, 30.9–475.3). Moreover, breast cancer with DMF (n = 4, 62.8, 20.5–191.9) and hypothyroidism with Cladr (n = 3; 89.2, 25.9–307.5) were also unexpected. The reporting of drugs-related ADRs in MS were mostly reported in the literature, but some unknown ADRs were also found. However, further studies are necessary to increase the awareness about the safety profiles of new drugs on the market.

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Section: Discussionmentioning

confidence: 99%

Adverse Drug Reactions with Drugs Used in Multiple Sclerosis: An Analysis from the Italian Pharmacovigilance Database

et al. 2022

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“…HDL lipoproteins are generally believed to be an atheroprotective component of plasma lipoproteins, but not all HDL subfractions exhibit this protective funtion. Some studies report potential atherogenic properties of small HDL subfractions [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

The impact of sleep apnea syndrome on the altered lipid metabolism and the redox balance

et al. 2021

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Background Obstructive sleep apnea (OSA) is a disorder with a significant risk for cardiovascular diseases. Dyslipidemia and redox imbalance belong to potential mechanisms linking OSA with the development of vascular diseases. The main aim of this study was the evaluation of the presence of lipid abnormalities in OSA patients, focusing on small dense low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions and determination of the redox imbalance by evaluating the marker of oxidative damage to plasma lipids - lipoperoxides. Methods The study included 15 male subjects with polysomnographically confirmed OSA and 16 male healthy controls. Plasma levels of total cholesterol, LDL and HDL and their subfractions, triacylglycerols and lipoperoxides were determined in all study individuals. Plasma LDL and HDL subfractions were separated by the Lipoprint system which is a polyacrylamide gel electrophoresis. Lipoperoxide levels were determined spectrophotometrically. Results OSA patients had significantly higher triacylglycerols, total cholesterol and LDL-cholesterol compared to healthy controls. HDL cholesterol was not significantly different. Of the LDL and HDL subfractions, OSA patients had significantly lower levels of atheroprotective LDL1 and large HDL subfractions and significantly higher levels of atherogenic small dense LDL3–7 and HDL8–10 subfractions. Lipoperoxide levels in patients with OSA were significantly elevated compared to healthy individuals. Conclusion The lipoprotein pro-atherogenic phenotype was found in individuals with OSA characterized by increased levels of atherogenic lipoprotein subfractions and reduced levels of atheroprotective subfractions. In addition, a plasma redox imbalance was found in patients with OSA compared to controls by detecting higher oxidative damage to lipids. Abnormalities in lipoprotein levels in patients with OSA, as well as the redox imbalance, could lead to an acceleration of the atherosclerotic process in predisposed individuals and thus represent a significant risk factor for vasular diseases.

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“…This study has several limitations. First, the major lipid fractions (HDL-C, LDL-C and TG) are each heterogeneous groups of particles defined by differences in particle size, density, apoprotein content, migration characteristics and relationships to disease, and these subfractions differ in their risk profiles 45 . This study was designed to investigate total blood lipid levels and thus did not consider whether there are subtypes of these fractions (e.g.…”

Section: Limitationsmentioning

confidence: 99%

“…This study was designed to investigate total blood lipid levels and thus did not consider whether there are subtypes of these fractions (e.g. LDL sub-particles) 45, 46 that might play different roles in MS risk or severity. Second The current study is unable to determine the underlying mechanism(s) for the potential causal relationship between RAC2 and MS risk; however, it is hoped that the findings presented may motivate further basic science investigations.…”

Section: Limitationsmentioning

confidence: 99%

Exploring the Role of Plasma Lipids and Statins Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study

ALMRAMHI

Finan

Storm

et al. 2022

Preprint

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Background There has been considerable interest in statins due to their pleiotropic effects beyond their lipid-lowering properties. Many of these pleiotropic effects are predominantly ascribed to their capacity to inhibit the isoprenylation of Rho small guanosine triphosphatases (Rho GTPases). We aimed to genetically investigate the role of lipids and statin interventions on multiple sclerosis (MS) risk and severity. Method We employed two-sample Mendelian randomization (MR) to: (1) investigate the causal role of lipids (high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG)) levels in MS risk and severity, (2) genetically mimic both cholesterol-dependent (via low-density lipoprotein cholesterol (LDL-C) and cholesterol biosynthesis pathway) and cholesterol-independent (via Rho GTPases) effects of statins on MS risk and MS severity. Results The results of MR using the inverse variance weighted method show that lifelong higher HDL-C (OR 1.14 (95% CI 1.04 to1.26), p-value 7.94E-03) increase MS risk, but LDL-C and TG were not. MR results also show that genetically predicted RAC2 (OR 0.86 (95% CI 0.78 to 0.95), p-value 3.80E-03) is implicated causally in reducing MS risk. Furthermore, we found no evidence for the causal role of lipids and genetically mimicked statins on MS severity. There is no evidence of reverse causation between MS risk and lipids. Conclusions Evidence from this study suggests that HDL-C is a risk factor for MS development. The MR findings suggest that RAC2 (a member of Rho GTPases) is a potent genetic modifier of MS risk. Since RAC2 has been reported to mediate some of the pleiotropic effects of statins, we suggest that statins reduce MS risk via a RAC2-related mechanism(s) (i.e., cholesterol-independent pathway).

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Lipoprotein profiling in early multiple sclerosis patients: effect of chronic inflammation?

Cited by 16 publications

References 47 publications

Adverse Drug Reactions with Drugs Used in Multiple Sclerosis: An Analysis from the Italian Pharmacovigilance Database

Adverse Drug Reactions with Drugs Used in Multiple Sclerosis: An Analysis from the Italian Pharmacovigilance Database

The impact of sleep apnea syndrome on the altered lipid metabolism and the redox balance

Exploring the Role of Plasma Lipids and Statins Interventions on Multiple Sclerosis Risk and Severity: A Mendelian Randomization Study

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