4.7 Review

Proprotein Convertase Subtilisin/Kexin 9 as a Modifier of Lipid Metabolism in Atherosclerosis

Related references

Note: Only part of the references are listed.
Article Cell Biology

Targeting PCSK9 in Liver Cancer Cells Triggers Metabolic Exhaustion and Cell Death by Ferroptosis

Malak Alannan et al.

Summary: The inhibition of PCSK9 in liver cancer cells can effectively suppress cell proliferation and enhance vulnerability to iron-triggered lipid peroxidation. Targeting the key metabolic player PCSK9 may be a potential therapeutic approach for treating liver cancers.

CELLS (2023)

Review Biochemistry & Molecular Biology

Emerging Insights on the Diverse Roles of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Chronic Liver Diseases: Cholesterol Metabolism and Beyond

Thomas Grewal et al.

Summary: Chronic liver diseases are often associated with dysregulated cholesterol metabolism. PCSK9, synthesized and secreted by the liver, is a key regulator of circulating LDL cholesterol levels. In addition to its role in cholesterol homeostasis, PCSK9 has been found to be involved in various other cellular processes. Its additional roles beyond cholesterol homeostasis are crucial for liver physiology in health and disease. This review summarizes studies on PCSK9 levels in patients with chronic liver diseases, discussing the factors affecting PCSK9 levels, clinically relevant studies, and the pathophysiological role of PCSK9 in chronic liver injury.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Article Multidisciplinary Sciences

Caffeine blocks SREBP2-induced hepatic PCSK9 expression to enhance LDLR-mediated cholesterol clearance

Paul F. Lebeau et al.

Summary: Caffeine inhibits the activation of SREBP2 to promote LDLc clearance and reduce the risk of cardiovascular disease.

NATURE COMMUNICATIONS (2022)

Article Biochemistry & Molecular Biology

Gene Therapy Targeting PCSK9

Julius L. Katzmann et al.

Summary: Recent developments in cardiovascular prevention research have shown successful treatments for LDL hypercholesterolemia, such as inhibiting the PCSK9 gene or using specific drugs. These methods have led to long-term reductions in LDL cholesterol levels and have the potential to fundamentally change our approach to cardiovascular prevention.

METABOLITES (2022)

Article Biology

PCSK9 Promotes Cardiovascular Diseases: Recent Evidence about Its Association with Platelet Activation-Induced Myocardial Infarction

Meidi Utami Puteri et al.

Summary: Cardiovascular diseases, particularly heart failure caused by myocardial infarction, are the leading cause of death worldwide. Research on atherosclerosis prevention has been conducted to reduce the risk of myocardial infarction. Recent experimental studies have revealed the crucial role of PCSK9 in platelet activation and its involvement in atherosclerosis progression.

LIFE-BASEL (2022)

Article Medicine, General & Internal

Effect of PCSK9 Inhibitors on Hemostasis in Patients with Isolated Hypercholesterolemia

Marcin Basiak et al.

Summary: The study aimed to determine the efficacy of PCSK9 inhibitors in patients with isolated hypercholesterolemia. The results showed that PCSK9 inhibitors reduced plasma levels/activity of fibrinogen, factor VII, and plasminogen activator inhibitor-1, suggesting potential benefits for patients who cannot tolerate or are contraindicated for statin use.

JOURNAL OF CLINICAL MEDICINE (2022)

Article Cell Biology

PCSK9 Contributes to the Cholesterol, Glucose, and Insulin2 Homeostasis in Seminiferous Tubules and Maintenance of Immunotolerance in Testis

R. -Marc Pelletier et al.

Summary: This study investigated the role of PCSK9 in cholesterol and immunotolerance regulation, glucose and insulin response in the testis and hypophysis. Results showed that PCSK9 deficiency led to cholesterol accumulation, immune cell infiltration, and changes in immunotolerance in the testis. Additionally, glucose and insulin regulation were also affected by PCSK9 deficiency.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

Article Biochemistry & Molecular Biology

Insight into the Evolving Role of PCSK9

Mateusz Maliglowka et al.

Summary: PCSK9 is a serine protease synthesized in hepatic cells that plays a crucial role in cholesterol metabolism. Blocking PCSK9 activity with drugs can decrease cardiovascular risk, leading to further research on PCSK9.

METABOLITES (2022)

Article Cardiac & Cardiovascular Systems

PCSK9 inhibitors for secondary prevention in patients with cardiovascular diseases: a bayesian network meta-analysis

Xing Wang et al.

Summary: This study evaluated the benefit and safety of different types of PCSK9 inhibitors for secondary prevention in patients with high-risk of cardiovascular events. The results showed that alirocumab was associated with reduced all-cause mortality and decreased risk of serious adverse events, while evolocumab was associated with increased all-cause mortality compared to alirocumab.

CARDIOVASCULAR DIABETOLOGY (2022)

Review Peripheral Vascular Disease

Expanding Biology of PCSK9: Roles in Atherosclerosis and Beyond

Nabil G. Seidah et al.

Summary: Since the discovery of PCSK9 in 2003, it has been found to play roles not only in regulating LDL-cholesterol, but also in inflammation, pathogen infections, and cellular proliferation in various cancers and associated metastases.

CURRENT ATHEROSCLEROSIS REPORTS (2022)

Review Peripheral Vascular Disease

Inclisiran: How Widely and When Should We Use It?

Angela Pirillo et al.

Summary: In this review, the efficacy and safety of inclisiran, a siRNA targeting PCSK9, in reducing LDL-C levels is discussed. Randomized clinical trials have shown that inclisiran provides durable reductions of PCSK9 and LDL-C levels, with a dosing schedule of once every 6 months. These effects are consistent in different categories of patients, and the drug's safety profile is favorable.

CURRENT ATHEROSCLEROSIS REPORTS (2022)

Review Cell Biology

PCSK9 in Liver Cancers at the Crossroads between Lipid Metabolism and Immunity

Malak Alannan et al.

Summary: Metabolic rewiring and defective immune responses play important roles in many cancers. PCSK9, an atypical enzyme, regulates lipid metabolism by controlling LDLR and other cell surface receptors. Studies have also shown its involvement in the immune system and other physiological activities.

CELLS (2022)

Article Biochemistry & Molecular Biology

PCSK9 Affects Astrocyte Cholesterol Metabolism and Reduces Neuron Cholesterol Supplying In Vitro: Potential Implications in Alzheimer's Disease

Bianca Papotti et al.

Summary: The involvement of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Alzheimer's disease (AD) has been poorly investigated. This study found that PCSK9 can interfere with cholesterol metabolism between astrocytes and neurons, leading to a reduction in neuronal cholesterol and potentially harmful effects. Additionally, PCSK9 exhibited neurotoxicity. These findings suggest that PCSK9 could be a potential pharmacological target in the treatment of AD.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Review Cell Biology

PCSK9 Inhibition: From Current Advances to Evolving Future

Chunping Liu et al.

Summary: This article summarizes the application, preclinical studies, safety, mechanism of action, and latest research progress of PCSK9 inhibitors. It aims to provide ideas for drug research and development, as well as expand the application of PCSK9 inhibitors in other diseases.

CELLS (2022)

Article Cardiac & Cardiovascular Systems

Efficacy and Safety of Inclisiran in Patients with Polyvascular Disease: Pooled, Post Hoc Analysis of the ORION-9, ORION-10, and ORION-11 Phase 3 Randomized Controlled Trials

Wolfgang Koenig et al.

Summary: This study analyzed the lipid-lowering efficacy and safety of inclisiran versus placebo in patients with and without polyvascular disease (PVD). The results showed that twice-yearly inclisiran dosing effectively reduced LDL-C levels and was well tolerated in patients, irrespective of PVD status.

CARDIOVASCULAR DRUGS AND THERAPY (2022)

Article Biology

Association between the rs615563 variant of PCSK9 gene and circulating lipids and Type 2 diabetes

Samira Taghizadeh Jazdani et al.

Summary: The study found no significant association between the PCSK9 rs615563 variant and the incidence of type 2 diabetes. The distribution of genotypes and the incidence of diabetes were not significantly different between diabetic and non-diabetic individuals after five years of follow-up. Additionally, there was no significant relationship between this genetic variant and serum lipid parameters.

BMC RESEARCH NOTES (2021)

Article Biochemistry & Molecular Biology

A Systematic Approach to Assess the Activity and Classification of PCSK9 Variants

Kepa B. Uribe et al.

Summary: Research shows that GOF mutations of the PCS9 gene lead to familial hypercholesterolemia, while LOF mutations are associated with reduced cholesterol levels. By studying the effects of different PCS9 variants on LDLR expression and affinity through transient transfections of HEK293 and HepG2 cells, it is possible to reliably determine their GOF or LOF status.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Genetics & Heredity

Mutational Spectrum of LDLR and PCSK9 Genes Identified in Iranian Patients With Premature Coronary Artery Disease and Familial Hypercholesterolemia

Arman Moradi et al.

Summary: Genetic mutations in LDLR and PCSK9 genes exhibit diversity in Iranian patients with FH, potentially leading to the development of FH and early-onset CAD. A pathogenic mutation in the LDLR gene was found to be cosegregated in a family. Genetic testing and reports on nucleotide alterations are limited in the Iranian population.

FRONTIERS IN GENETICS (2021)

Article Cardiac & Cardiovascular Systems

Assessing the impact of PCSK9 inhibition on coronary plaque phenotype with optical coherence tomography: rationale and design of the randomized, placebo-controlled HUYGENS study

Stephen J. Nicholls et al.

Summary: The HUYGENS study aims to evaluate the impact of incremental lipid lowering using the PCSK9 inhibitor evolocumab on plaque features in ACS patients treated with statins. The study will use OCT imaging to assess the effects of evolocumab on coronary atherosclerotic plaques, with the primary endpoint being evaluated at baseline and week 50.

CARDIOVASCULAR DIAGNOSIS AND THERAPY (2021)

Review Cardiac & Cardiovascular Systems

Regulation of PCSK9 Expression and Function: Mechanisms and Therapeutic Implications

Xiao-dan Xia et al.

Summary: PCSK9 plays a vital role in promoting cardiovascular disease and cancer by degrading LDLR and affecting tumor growth. Inhibition of PCSK9 can reduce the risk of cardiovascular disease and cancer.

FRONTIERS IN CARDIOVASCULAR MEDICINE (2021)

Review Cardiac & Cardiovascular Systems

PCSK9 Functions in Atherosclerosis Are Not Limited to Plasmatic LDL-Cholesterol Regulation

Aureli Luquero et al.

Summary: The role of PCSK9 in atherosclerosis progression involves mechanisms such as lipid-lowering effects, regulation of key receptors in macrophages, and modulation of vascular inflammation. Inhibition of PCSK9 activity has been shown to reduce the progression of atherosclerotic disease.

FRONTIERS IN CARDIOVASCULAR MEDICINE (2021)

Review Biochemistry & Molecular Biology

PCSK9 Biology and Its Role in Atherothrombosis

Cristina Barale et al.

Summary: PCSK9 plays a key role in lipoprotein metabolism and atherosclerosis, with potential cardiovascular benefits from its inhibition. Currently, anti-PCSK9 antibodies and small interfering RNA are effective therapies to reduce LDL-C levels and attenuate cardiovascular disease.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Review Biochemistry & Molecular Biology

PCSK9: A Multi-Faceted Protein That Is Involved in Cardiovascular Biology

Sai Sahana Sundararaman et al.

Summary: PCSK9, primarily secreted by hepatocytes, plays a role in regulating the degradation of the LDL receptor. Its effects on cardiovascular complications are not only LDLR-related, but also involve other independent pathways and processes.

BIOMEDICINES (2021)

Review Peripheral Vascular Disease

An Update on the Role of PCSK9 in Atherosclerosis

Ece Yurtseven et al.

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS (2020)

Article Cardiac & Cardiovascular Systems

Clinical implications and outcomes of the ORION Phase III trials

Julia Brandts et al.

FUTURE CARDIOLOGY (2020)

Review Genetics & Heredity

PCSK9Variants in Familial Hypercholesterolemia: A Comprehensive Synopsis

Qianyun Guo et al.

FRONTIERS IN GENETICS (2020)

Review Biochemistry & Molecular Biology

Adaptive Immune Responses in Human Atherosclerosis

Silvia Lee et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

Article Cardiac & Cardiovascular Systems

Estimation of the major cardiovascular events prevention with Inclisiran

Alberto Cordero et al.

ATHEROSCLEROSIS (2020)

Review Medicine, Research & Experimental

LDL, LDL receptors, and PCSK9 as modulators of the risk for type 2 diabetes: a focus on white adipose tissue

May Faraj

JOURNAL OF BIOMEDICAL RESEARCH (2020)

Review Pharmacology & Pharmacy

Efficacy and safety of PCSK9 monoclonal antibodies: an evidence-based review and update

Rasha Kaddoura et al.

JOURNAL OF DRUG ASSESSMENT (2020)

Article Medicine, Research & Experimental

NLRP3 inflammasome via IL-1 13 regulates PCSK9 secretion

Zufeng Ding et al.

THERANOSTICS (2020)

Article Cardiac & Cardiovascular Systems

PCSK9 regulates expression of scavenger receptors and ox-LDL uptake in macrophages

Zufeng Ding et al.

CARDIOVASCULAR RESEARCH (2018)

Review Cardiac & Cardiovascular Systems

PCSK9 From Basic Science Discoveries to Clinical Trials

Michael D. Shapiro et al.

CIRCULATION RESEARCH (2018)

Article Multidisciplinary Sciences

PCSK9 induces a pro-inflammatory response in macrophages

Chiara Ricci et al.

SCIENTIFIC REPORTS (2018)

Article Peripheral Vascular Disease

Treatment patterns and patient characteristics among early initiators of PCSK9 inhibitors

Dionne M. Hines et al.

VASCULAR HEALTH AND RISK MANAGEMENT (2018)

Review Immunology

Monocyte-Macrophages and T Cells in Atherosclerosis

Ira Tabas et al.

IMMUNITY (2017)

Review Peripheral Vascular Disease

Lipid Lowering Therapy and Circulating PCSK9 Concentration

Tsuyoshi Nozue

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS (2017)

Article Cardiac & Cardiovascular Systems

Relationship of PCSK9 and Urinary Thromboxane Excretion to Cardiovascular Events in Patients With Atrial Fibrillation

Daniele Pastori et al.

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY (2017)

Article Medicine, General & Internal

Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol

Kausik K. Ray et al.

NEW ENGLAND JOURNAL OF MEDICINE (2017)

Review Pharmacology & Pharmacy

Regulation of PCSK9 by nutraceuticals

Amir Abbas Momtazi et al.

PHARMACOLOGICAL RESEARCH (2017)

Review Medicine, General & Internal

PCSK9 signaling pathways and their potential importance in clinical practice

Michal Wicinski et al.

EPMA JOURNAL (2017)

Article Cardiac & Cardiovascular Systems

New role of PCSK9 in atherosclerotic inflammation promotion involving the TLR4/NF-κB pathway

Zhi-Han Tang et al.

ATHEROSCLEROSIS (2017)

Review Cardiac & Cardiovascular Systems

Physiological and therapeutic regulation of PCSK9 activity in cardiovascular disease

Simon Glerup et al.

BASIC RESEARCH IN CARDIOLOGY (2017)

Article Cardiac & Cardiovascular Systems

Human PCSK9 promotes hepatic lipogenesis and atherosclerosis development via apoE- and LDLR-mediated mechanisms

Hagai Tavori et al.

CARDIOVASCULAR RESEARCH (2016)

Review Pharmacology & Pharmacy

Unmet Needs in LDL-C Lowering: When Statins Won't Do!

Stephan Krahenbuhl et al.

DRUGS (2016)

Article Biochemistry & Molecular Biology

PCSK9 inhibition-mediated reduction in Lp(a) with evolocumab: an analysis of 10 clinical trials and the LDL receptor's role

Frederick J. Raal et al.

JOURNAL OF LIPID RESEARCH (2016)

Article Peripheral Vascular Disease

The Relationship between the Plasma PCSK9 Levels and Platelet Indices in Patients with Stable Coronary Artery Disease

Sha Li et al.

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS (2015)

Review Biochemistry & Molecular Biology

PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells

Thomas A. Lagace

CURRENT OPINION IN LIPIDOLOGY (2014)

Article Biochemistry & Molecular Biology

Internalized PCSK9 dissociates from recycling LDL receptors in PCSK9-resistant SV-589 fibroblasts

My-Anh Nguyen et al.

JOURNAL OF LIPID RESEARCH (2014)

Article Cell Biology

The Nuclear Factor NF-κB Pathway in Inflammation

Toby Lawrence

COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY (2009)

Article Multidisciplinary Sciences

Molecular basis for LDL receptor recognition by PCSK9

Hyock Joo Kwon et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)