Effects of lipoprotein apheresis on PCSK9 levels

Julius, Ulrich; Milton, Mark; Stoellner, Daniela; Rader, Daniel J.; Gordon, Bruce R.; Polk, Donna M.; Waldmann, Elisa; Parhofer, Klaus G.; Moriarty, Patrick M.

doi:10.1016/j.atherosclerosissup.2015.02.028

Cited by 23 publications

(19 citation statements)

References 30 publications

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“…The deletion of the LDLR gene in familial hypercholesterolemia may be an important event in the pathogenesis of the disease [28]. A previous study showed that lipid plasmapheresis could reduce plasma PCSK9 levels [29]. Similarly, our study showed that lipid plasmapheresis could induce downregulation of the PCSK9 protein in isolated PBMCs.…”

Section: Changes In Lipid Metabolic Proteins (Cd36 Pcsk9 and Ldlr)supporting

confidence: 72%

Plasma purification is associated with reduced inflammation factors and down-regulation of lipid metabolic and ER stress proteins in patients with hyperlipidemia

Zhang

Deng

et al. 2020

Preprint

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BackgroundHyperlipidaemia is a strong risk factor for arteriosclerosis and cardiovascular disease (CVD). Therapy with lipid-lowering drugs often results in many side effects. The aim of our study was to investigate the potential effects of non-drug therapy with double-filtration plasmapheresis (DFPP) on lipid metabolism-, endoplasmic reticulum (ER) stress- and apoptosis-related proteins in peripheral blood mononuclear cells (PBMCs) before and after lipid clearance in patients with hyperlipidaemia.MethodsThirty-five patients with hyperlipidaemia were selected for this study. Proteins related to lipid metabolism [CD36, proprotein convertase subtilisin/kexin type 9 (PCSK9) and LDL receptor], ER stress [glucose-regulated protein 78 (GRP78), C/EBP homoiogousprotein (CHOP), activating transcription factor 4 (ATF4), eukaryotic initiation factor 2 (EIF2a)] and apoptosis (Bcl-2, BAX, and Caspase-3) were assayed by western blot, reactive oxygen species (ROS) were measured by flow cytometry (FCM), and serum inflammatory factors were detected by ELISA.ResultsCompared with their pre-DFPP values, the values of most lipid metabolic parameters, such as cholesterol, triglycerides, LDL, lipoprotein a [Lp(a)] and small dense LDL cholesterol (sdLDL), were reduced after DFPP. DFPP was associated with the downregulation of proteins related to lipid metabolism, ER stress and apoptosis, which also resulted in decreased ROS and serum inflammatory factor release.ConclusionDFPP has lipid-lowering activity and can also regulate lipid metabolism-, ER stress- and apoptosis-related proteins in PBMCs and reduce the levels of inflammatory factors in patients with hyperlipidaemia (ClinicalTrials.gov number: NCT03491956).

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Section: Changes In Lipid Metabolic Proteins (Cd36 Pcsk9 and Ldlr)supporting

confidence: 72%

Plasma purification is associated with reduced inflammation factors and down-regulation of lipid metabolic and ER stress proteins in patients with hyperlipidemia

Zhang

Deng

et al. 2020

Preprint

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“…The deletion of LDLR gene in familial hypercholesterolemia may be an important link in the pathogenesis of the disease [28]. Previous study showed that lipid plasmapheresis could reduce plasma PCSK9 levels [29]. Similarly, our study showed lipid plasmapheresis could induce a down-regulation of PCSK9 protein in isolated PBMC.…”

Section: Changes Of Lipid Metabolic Proteins Cd36 Pcsk9 Ldlrsupporting

confidence: 71%

Plasma Purification is Associated With Reduced Inflammation Factors and Down-regulation of Lipid Metabolic and ER Stress Proteins in Patients With Hyperlipidemia

Zhang

Deng

et al. 2020

Preprint

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Background Hyperlipidemia is a strong risk factor for arteriosclerosis and cardiovascular disease (CVD). Lipid-lowering therapy using drugs often results in many side effects. The aim of our study is to investigate the potential effects of non-drug therapy by double filtration plasmapheresis (DFPP) on lipid metabolic, endoplasmic reticulum (ER) stress and apoptosis related proteins in peripheral blood mononuclear cells (PBMC) before and after lipid clear out in patients with hyperlipidemia. MethodsLipid metabolic [CD36, propotein convertase subtilisin/kexin type 9 (PCSK9) and LDL receptor], ER stress (GRP78, CHOP, ATF4, EIF2a) and apoptosis related (Bcl-2, BAX, and Caspase-3) proteins were assayed by western blot, reactive oxygen species (ROS) measured by flow cytometry (FCM) and serum inflammatory factors were detected by ELISA. Results35 patients with hyperlipidemia were selected into this study. Compared with pre-DFPP, most of lipid metabolic parameters as cholesterol, triglyceride, LDL, lipoprotein a [Lp(a)] and small dense LDL cholesterol (sdLDL) reduced. DFPP process was associated with the down-regulation of lipid metabolic, ER stress and apoptosis proteins, also resulted in the decrease in ROS and serum inflammatory factors release. Conclusion DFPP owns the capacity of lipid-lowering, also can regulate lipid metabolic, ER stress and apoptosis related proteins in PBMC and reduce inflammatory factors in patients with hyperlipidemia (ClinicalTrials.gov number, NCT03491956). Footnote: Xiao Meng Zhang and Hao Deng contribute equally to this paper.

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“…At least, an acute reduction of fibrinogen improves blood flow, and a decrease of C-reactive protein may have an anti-inflammatory effect. However, some effects are rather short-lasting (for instance on PCSK9 [ 26 ], on cytokines).…”

Section: Lipoprotein Apheresis—what Is the Evidencementioning

confidence: 99%

Current Role of Lipoprotein Apheresis in the Treatment of High-Risk Patients

Julius

2018

JCDD

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Lipoprotein apheresis (LA) is a therapeutic approach to save the lives of patients who are at an extremely high risk of developing cardiovascular events (CVE), especially after all other therapeutic options were not tolerated, or appeared not to be effective enough. Homozygous familial hypercholesterolemia represents a clear indication to start LA therapy. Another recognized indication is a severe hypercholesterolemia, which induced CVE, often in association with other risk factors. In the last years, an expressive elevation of lipoprotein(a) (Lp(a)) emerged as an indication for LA. In Germany, progress of atherosclerosis should have been documented before the permission to start LA therapy is given in these patients. Usually, all LA methods acutely decrease both LDL-C and Lp(a). However, specific columns which reduce only Lp(a) are available. Case reports and prospective observations comparing the situation before and during LA therapy clearly show a high efficiency with respect to the reduction of CVE, especially in patients with high Lp(a) levels. PCSK9 inhibitors may reduce the need for LA in patients with heterozygous or polygenetic hypercholesterolemia, but in some patients, a combination of these drugs with LA will be necessary. In the future, an antisense oligonucleotide against apolipoprotein(a) may offer an alternative therapeutic approach.

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Effects of lipoprotein apheresis on PCSK9 levels

Cited by 23 publications

References 30 publications

Plasma purification is associated with reduced inflammation factors and down-regulation of lipid metabolic and ER stress proteins in patients with hyperlipidemia

Plasma purification is associated with reduced inflammation factors and down-regulation of lipid metabolic and ER stress proteins in patients with hyperlipidemia

Plasma Purification is Associated With Reduced Inflammation Factors and Down-regulation of Lipid Metabolic and ER Stress Proteins in Patients With Hyperlipidemia

Current Role of Lipoprotein Apheresis in the Treatment of High-Risk Patients

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