scholarly journals Multiparametric assessment of cellular lipid metabolism in hypercholesterolemia

2021 ◽  
Author(s):  
Simon G. Pfisterer ◽  
Ivonne Brock ◽  
Kristiina Kanerva ◽  
Iryna Hlushchenko ◽  
Lassi Paavolainen ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Density Lipoprotein ◽  
Lipid Uptake ◽  
Cellular Lipid ◽  
Peripheral Blood Mononuclear ◽  
Lipid Mobilization ◽  
Polygenic Scores ◽  
Ldl Uptake

AbstractDifferences in cellular lipid metabolism may underlie large interindividual variability in lipid disorders such as hypercholesterolemia. Here, we established a multi-parametric imaging platform enabling the quantification of lipid uptake and storage in cytoplasmic droplets of leukocyte populations from 2-4 ml of peripheral blood. We define a new quantifiable parameter, cellular lipid mobilization, describing the efficiency at which cells deplete their lipid reservoirs. The 65 individuals studied, including heterozygous familial hypercholesterolemia (He-FH) patients with identical LDL receptor mutations, showed distinct profiles of low-density lipoprotein (LDL) uptake and lipid mobilization. Lipid mobilization correlated positively with cellular LDL uptake and negatively with hypercholesterolemia, increased body mass index and age. Lipid mobilization and LDL uptake distinguished good and poor statin responders among He-FH patients, and their combination with polygenic scores improved the risk assessment in hypercholesterolemia within a general population subcohort. Together, these findings open up new avenues for personalized medicine approaches in hypercholesterolemia.Abstract FigureGraphical abstractSchematic illustration of functional readouts in peripheral blood mononuclear cells and their correlation with physiological outcomes in monogenic and polygenic hypercholesterolemia.

scholarly journals Statin-induced microRNAome alterations modulating inflammation pathways of peripheral blood mononuclear cells in patients with hypercholesterolemia

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Hung-Ju Lin ◽  
Sung-Liang Yu ◽  
Ta-Chen Su ◽  
Hsiu-Ching Hsu ◽  
Ming-Fong Chen ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Transforming Growth Factor ◽  
Quantitative Polymerase Chain Reaction ◽  
Density Lipoprotein ◽  
Cardiovascular Risks ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Abstract Statins inhibit cholesterol biogenesis and modulate atheroma inflammation to reduce cardiovascular risks. Promoted by immune and non-immune cells, serum C-reactive protein (CRP) might be a biomarker suboptimal to assess inflammation status. Although it has been reported that statins modulated inflammation via microRNAs (miRNAs), evidence remains lacking on comprehensive profiling of statin-induced miRNAome alterations in immune cells. We recruited 19 hypercholesterolemic patients receiving 2 mg/day pitavastatin and 15 ones receiving 10 mg/day atorvastatin treatment for 12 weeks, and performed microarray-based profiling of 1733 human mature miRNAs in peripheral blood mononuclear cells (PBMCs) before and after statin treatment. Differentially expressed miRNAs were determined if their fold changes were >1.50 or <0.67, after validated using quantitative polymerase chain reaction (qPCR). The miRSystem and miTALOS platforms were utilized for pathway analysis. Of the 34 patients aged 63.7 ± 6.2 years, 27 were male and 19 were with coronary artery disease. We discovered that statins induced differential expressions of miR-483-5p, miR-4667-5p, miR-1244, and miR-3609, with qPCR-validated fold changes of 1.74 (95% confidence interval, 1.33–2.15), 1.61 (1.25–1.98), 1.61 (1.01–2.21), and 1.68 (1.19–2.17), respectively. The fold changes of the four miRNAs were not correlated with changes of low-density-lipoprotein cholesterol or CRP, after sex, age, and statin type were adjusted. We also revealed that RhoA and transforming growth factor-β signaling pathways might be regulated by the four miRNAs. Given our findings, miRNAs might be involved in statin-induced inflammation modulation in PBMCs, providing likelihood to assess and reduce inflammation in patients with atherosclerotic cardiovascular diseases.

scholarly journals Daily intake of heat-killed Lactobacillus plantarum L-137 improves inflammation and lipid metabolism in overweight healthy adults: a randomized-controlled trial

2019 ◽  
Vol 59 (6) ◽  
pp. 2641-2649 ◽  
Author(s):  
Yusuke Tanaka ◽  
Yoshitaka Hirose ◽  
Yoshihiro Yamamoto ◽  
Yasunobu Yoshikai ◽  
Shinji Murosaki
Keyword(s):  
Lipid Metabolism ◽  
Lactobacillus Plantarum ◽  
Mononuclear Cells ◽  
Controlled Trial ◽  
Low Density Lipoprotein ◽  
Daily Intake ◽  
Density Lipoprotein ◽  
Control Group ◽  
Double Blind ◽  
Peripheral Blood Mononuclear

Abstract Purpose The effects of heat-killed Lactobacillus plantarum L-137 (HK L-137) on inflammation and lipid metabolism were investigated in overweight volunteers. Methods One hundred healthy subjects with a body mass index from 23.0 to 29.9 (51 men and 49 women; mean age: 41.4 years) were enrolled in this randomized, double-blind, placebo-controlled, parallel group study. Subjects were randomly assigned to daily administration of a tablet containing HK L-137 (10 mg) or a placebo tablet for 12 weeks. Blood samples were collected every 4 weeks to measure biomarkers of lipid metabolism and inflammatory mediators. Results The percent change of concanavalin A-induced proliferation of peripheral blood mononuclear cells was significantly larger in the HK L-137 group than in the control group, similar to previous studies. The decreases of aspartate aminotransferase and alanine aminotransferase over time were significantly larger in the HK L-137 group than in the control group, as were the decreases of total cholesterol, low-density lipoprotein cholesterol, and the leukocyte count at one time point. These effects of HK L-137 were stronger in the subjects with higher C-reactive protein levels. Conclusions These findings suggest that daily intake of HK L-137 can improve inflammation and lipid metabolism in subjects at risk of inflammation.

scholarly journals Spectrally and Time-Resolved Fluorescence Imaging of 22-NBD-Cholesterol in Human Peripheral Blood Mononuclear Cells in Chronic Kidney Disease Patients

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6800
Author(s):  
Ingrid Lajdova ◽  
Livia Ovsonkova ◽  
Viera Spustova ◽  
Adrian Oksa ◽  
Dusan Chorvat ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Lipid Metabolism ◽  
Kidney Disease ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Peripheral Blood Mononuclear ◽  
Time Resolved ◽  
Blood Mononuclear Cells

The interaction of the fluorescent probe 22-NBD-cholesterol with membranes of human peripheral blood mononuclear cells (PBMC) was tested by time- and spectrally resolved fluorescence imaging to monitor the disturbance of lipid metabolism in chronic kidney disease (CKD) and its treatment with statins. Blood samples from healthy volunteers (HV) and CKD patients, either treated or untreated with statins, were compared. Spectral imaging was done using confocal microscopy at 16 spectral channels in response to 458 nm excitation. Time-resolved imaging was achieved by time-correlated single photon counting (TCSPC) following excitation at 475 nm. The fluorescence of 22-NBD-cholesterol was mostly integrated into plasmatic membrane and/or intracellular membrane but was missing from the nuclear region. The presence of two distinct spectral forms of 22-NBD-cholesterol was uncovered, with significant variations between studied groups. In addition, two fluorescence lifetime components were unmasked, changing in CKD patients treated with statins. The gathered results indicate that 22-NBD-cholesterol may serve as a tool to study changes in the lipid metabolism of patients with CKD to monitor the effect of statin treatment.

scholarly journals The Synergistic Effect of Fluvastatin and IFN-λ on Peripheral Blood Mononuclear Cells of Chronic Hepatitis C Virus (HCV) Patients with IL-28B rs12979860 CC Genotype

2019 ◽  
Author(s):  
Amin Farzanegan Gharabolagh ◽  
Taravat Bamdad ◽  
Mehdi Hedayati ◽  
Seyed Ali Dehghan Manshadi
Keyword(s):  
Hepatitis C Virus ◽  
Lipid Metabolism ◽  
Hepatitis C ◽  
Mrna Expression ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Rna Extraction ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

  There is a relationship between the life cycle of the hepatitis C virus (HCV) and the synthesis and hemostasis of lipids as well as lipid metabolism and interferon (IFN) regulatory system. This study aimed to examine the effect of fluvastatin and IFN-ƛ in the expression of mediators involved in lipid metabolism and HCV proliferation in patients with rs12979860 CC polymorphism. Thirteen patients with HCV and five controls with rs1297986CC polymorphism were included in this study. Peripheral blood mononuclear cells (PBMCs) of patients and controls were treated by fluvastatin, IFN-λ or fluvastatin+IFN-λ. Assessment of IL-28B polymorphism, RNA extraction, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed. The mRNA expression of sterol regulatory element-binding protein 1 c (SREBP1c), ATP-binding cassette transporter A1 (ABCA1), diacylglycerol acyltransferase 1 (DGAT1), and HCV core as well as measurement of ABCA1 protein level were evaluated before and after treatment. The results indicated that IFN-λ +fluvastatin acted as an inhibitor in mRNA expression of SREBP1c; while acting as an inducer in the expression of ABCA-1. The results of ABCA1 assay showed a significant increase of this protein after treatment with fluvastatin and IFN-λ compared with untreated cells (p=0.02). Moreover, the mRNA expression of HCV core was suppressed in all experimental groups treated with fluvastatin, IFN-λ or their combination which was more significant after treatment with fluvastatin+IFN-λ (p<0.001). The results of this study demonstrated the significant effect of treatment with fluvastatin+IFN-λ in PBMCs of HCV patients with rs12979860 CC polymorphism. According to the drug resistance of viruses and prevention of virus-induced steatosis in patients with HCV, using regulatory agents of lipid mediators in parallel with current medications could be considered as an effective therapeutic strategy.

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