Effects of Alirocumab on Triglyceride Metabolism: A Fat-Tolerance Test and Nuclear Magnetic Resonance Spectroscopy Study

Metzner, Thomas; Leitner, Deborah R.; Mellitzer, Karin; Beck, Andrea M.; Sourij, Harald; Stojaković, Tatjana; Reishofer, Gernot; März, Winfried; Landmesser, Ulf; Scharnagl, Hubert; Toplak, Hermann; Silbernagel, Günther

doi:10.3390/biomedicines10010193

Cited by 4 publications

(4 citation statements)

References 43 publications

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“…Indeed, circulating PCSK9 remains bound to the therapeutic antibody for 2 to 3 weeks [ 31 ]. Nevertheless, total serum PCSK9 levels increased approximately 10-fold after 6 months of treatment with PCSK9 inhibitors, similar to previous studies [ 31 , 32 ]. Studies measuring only free circulating PCSK9 (without inactive PCSK9 bound to the therapeutic antibody) showed a decrease in PCSK9 levels after treatment with PCSK9 inhibitors [ 33 ].…”

Section: Discussionsupporting

confidence: 91%

“…Recently, preliminary results from the ALIROCKS study reported that total plasma PCSK9 levels could serve as a biomarker for adherence to treatment with PCSK9 antibodies. They suggested that in non-adherent patients, LDL-C levels should decrease by no more than 25% and total PCSK9 levels should increase by no more than threefold after treatment with PCSK9 inhibitors [ 32 ]. Based on these criteria, we identified three non-adherent patients in our cohort.…”

Section: Discussionmentioning

confidence: 99%

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Interplay between microRNAs, Serum Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), and Lipid Parameters in Patients with Very High Lipoprotein(a) Treated with PCSK9 Inhibitors

Levstek

Karun

Likozar

et al. 2023

Genes

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Proprotein convertase subtilisin/kexin type 9 (PCSK9) has an important function in the regulation of lipid metabolism. PCSK9 reduces hepatic low-density lipoprotein receptors, thereby increasing low-density lipoprotein cholesterol levels. However, its regulation remains to be elucidated, including post-transcriptional regulation by microRNAs (miRNAs). We aimed to explore the interplay between miRNAs, total serum PCSK9, and lipids during treatment with PCSK9 inhibitors. A total of 64 patients with stable coronary artery disease and very high lipoprotein(a) levels and 16 sex- and age-matched control subjects were enrolled. Patients received a PCSK9 inhibitor (evolocumab or alirocumab). Total serum PCSK9 levels were measured by immunoassay. RNA was isolated from plasma using magnetic beads, and expression of selected miRNAs was analyzed by quantitative PCR. Total serum PCSK9 levels were significantly higher in control subjects compared with patients. After 6 months of treatment with PCSK9 inhibitors, total serum PCSK9 levels increased significantly. The expression of miR-191-5p was significantly lower, and the expression of miR-224-5p and miR-483-5p was significantly higher in patients compared with control subjects. Using linear regression, the expression of miR-483-5p significantly predicted the serum PCSK9 level at baseline. After the 6-month period of therapy, the expression of miR-191-5p and miR-483-5p significantly increased. Our results support a role for miR-483-5p in regulating circulating PCSK9 in vivo. The difference in expression of miR-191-5p, miR-224-5p, and miR-337-3p between patients and control subjects suggests their possible role in the pathogenesis of coronary artery disease.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Interplay between microRNAs, Serum Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), and Lipid Parameters in Patients with Very High Lipoprotein(a) Treated with PCSK9 Inhibitors

Levstek

Karun

Likozar

et al. 2023

Genes

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“…Weighted-average lipoprotein particle sizes are derived from the sum of the diameter of each subclass multiplied by its relative mass percentage based on the amplitude of its methyl NMR signal [ 4 ]. The Numares AG (Am Biopark 9, 93053 Regensburg, Germany) performed NMR analysis using the AXINON ® lipoFIT ® method (in the further text briefly lipofit) in Regensburg with an Avance III HD nuclear magnetic resonance spectrometer (Bruker; Billerica, MA, USA), an Ascend 600 MHz magnet (Bruker), and using TopSpin 3.2 (Bruker) and Axinon Suite 1.0.0.1 (Numares, Regensburg, Germany) software [ 12 , 17 ].…”

Section: Methodsmentioning

confidence: 99%

Comparison of Two Nuclear Magnetic Resonance Spectroscopy Methods for the Measurement of Lipoprotein Particle Concentrations

et al. 2022

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Background: Measuring lipoprotein particle concentrations may help to improve cardiovascular risk stratification. Both the lipofit (Numares) and lipoprofile (LabCorp) NMR methods are widely used for the quantification of lipoprotein particle concentrations. Objective: The aim of the present work was to perform a method comparison between the lipofit and lipoprofile NMR methods. In addition, there was the objective to compare lipofit and lipoprofile measurements of standard lipids with clinical chemistry-based results. Methods: Total, LDL, and HDL cholesterol and triglycerides were measured with ß-quantification in serum samples from 150 individuals. NMR measurements of standard lipids and lipoprotein particle concentrations were performed by Numares and LabCorp. Results: For both NMR methods, differences of mean concentrations compared to ß-quantification-derived measurements were ≤5.5% for all standard lipids. There was a strong correlation between ß-quantification- and NMR-derived measurements of total and LDL cholesterol and triglycerides (all r > 0.93). For both, the lipofit (r = 0.81) and lipoprofile (r = 0.84) methods, correlation coefficients were lower for HDL cholesterol. There was a reasonable correlation between LDL and HDL lipoprotein particle concentrations measured with both NMR methods (both r > 0.9). However, mean concentrations of major and subclass lipoprotein particle concentrations were not as strong. Conclusions: The present analysis suggests that reliable measurement of standard lipids is possible with these two NMR methods. Harmonization efforts would be needed for better comparability of particle concentration data.

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“…The influence of alirocumab (PCSK9 antibodies) treatment on the metabolism of triglycerides was studied, with no significant effects being found on the levels of fasting triglycerides, post-prandial triglycerides, or proteins related to the regulation of lipoprotein lipase [26]. The short-term influence of alirocumab on vascular function has been studied, with no significant changes observed in the thickness of the carotid intima-media, brachial artery flow-dependent dilatation, or carotid artery fractional anisotropy [27].…”

mentioning

confidence: 99%

Lipids and Lipoproteins in Atherosclerosis

et al. 2023

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Effects of Alirocumab on Triglyceride Metabolism: A Fat-Tolerance Test and Nuclear Magnetic Resonance Spectroscopy Study

Cited by 4 publications

References 43 publications

Interplay between microRNAs, Serum Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), and Lipid Parameters in Patients with Very High Lipoprotein(a) Treated with PCSK9 Inhibitors

Interplay between microRNAs, Serum Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), and Lipid Parameters in Patients with Very High Lipoprotein(a) Treated with PCSK9 Inhibitors

Comparison of Two Nuclear Magnetic Resonance Spectroscopy Methods for the Measurement of Lipoprotein Particle Concentrations

Lipids and Lipoproteins in Atherosclerosis

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