Abstract
The inverse relationship between low plasma high-density lipoprotein cholesterol (HDL-C) concentrations and increased risk of Atherosclerotic Cardiovascular Disease (ASCVD) is well-known. However, plasma HDL-C concentrations are highly variable in subjects with ASCVD. In clinical outcome trials, pharmacotherapies that increase HDL-C concentrations are not associated with a reduction in ASCVD events. A causal relationship between HDL-C and ASCVD has also been questioned by Mendelian randomization studies and genome-wide association studies of genetic variants associated with plasma HDL-C concentrations. The U-shaped association between plasma HDL-C concentrations and mortality observed in several epidemiological studies implicates both low and very high plasma HDL-C concentrations in the etiology of ASCVD and non- ASCVD mortality. These data do not collectively support a causal association between HDL-C and ASCVD risk. Therefore, the hypothesis concerning the association between HDL and ASCVD has shifted from focus on plasma concentrations to the concept of functionality, in particular cellular cholesterol efflux and HDL holoparticle transport. In this review, we focus on these new concepts and provide a new framework for understanding and testing the role of HDL in ASCVD.
Keywords: High-density lipoprotein, atherosclerosis, plasma, cholesterol efflux, genome wide associations, apoA-I.
Current Medicinal Chemistry
Title:The Yin and Yang of High-density Lipoprotein and Atherosclerotic Cardiovascular Disease: Focusing on Functionality and Cholesterol Efflux to Reframe the HDL Hypothesis
Volume: 28 Issue: 29
Author(s): Shiva Ganjali, Gerald F. Watts, Maciej Banach, Željko Reiner, Petr Nachtigal and Amirhossein Sahebkar*
Affiliation:
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad,Iran
Keywords: High-density lipoprotein, atherosclerosis, plasma, cholesterol efflux, genome wide associations, apoA-I.
Abstract: The inverse relationship between low plasma high-density lipoprotein cholesterol (HDL-C) concentrations and increased risk of Atherosclerotic Cardiovascular Disease (ASCVD) is well-known. However, plasma HDL-C concentrations are highly variable in subjects with ASCVD. In clinical outcome trials, pharmacotherapies that increase HDL-C concentrations are not associated with a reduction in ASCVD events. A causal relationship between HDL-C and ASCVD has also been questioned by Mendelian randomization studies and genome-wide association studies of genetic variants associated with plasma HDL-C concentrations. The U-shaped association between plasma HDL-C concentrations and mortality observed in several epidemiological studies implicates both low and very high plasma HDL-C concentrations in the etiology of ASCVD and non- ASCVD mortality. These data do not collectively support a causal association between HDL-C and ASCVD risk. Therefore, the hypothesis concerning the association between HDL and ASCVD has shifted from focus on plasma concentrations to the concept of functionality, in particular cellular cholesterol efflux and HDL holoparticle transport. In this review, we focus on these new concepts and provide a new framework for understanding and testing the role of HDL in ASCVD.
Export Options
About this article
Cite this article as:
Ganjali Shiva , Watts F. Gerald , Banach Maciej , Reiner Željko , Nachtigal Petr and Sahebkar Amirhossein *, The Yin and Yang of High-density Lipoprotein and Atherosclerotic Cardiovascular Disease: Focusing on Functionality and Cholesterol Efflux to Reframe the HDL Hypothesis, Current Medicinal Chemistry 2021; 28 (29) . https://dx.doi.org/10.2174/0929867328666210208182326
DOI https://dx.doi.org/10.2174/0929867328666210208182326 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Fragile X Mental Retardation Protein: Past, Present and Future
Current Protein & Peptide Science In Vivo Uptake of β-Amyloid by Non-Plaque Associated Microglia
Current Alzheimer Research SUMOylation in Neurological Diseases
Current Molecular Medicine ZD6474, a Small Molecule Tyrosine Kinase Inhibitor, Potentiates the Anti-Tumor and Anti-Metastasis Effects of Radiation for Human Nasopharyngeal Carcinoma
Current Cancer Drug Targets Effect of Administration of Nandrolone Decanoate upon Aldosterone Concentration and Serum Na+/K+ Levels in Albino Mice
Cardiovascular & Hematological Agents in Medicinal Chemistry Thrombin Inhibition by the Highly Selective ‘ Reversible Suicide Substrate ’ N-Ethoxycarbonyl-D-Phenylalanyl-L-Prolyl-α-Azalysine p-Nitrophenyl Ester
Protein & Peptide Letters The Role of Antithrombotic Therapy in Heart Failure
Current Pharmaceutical Design Platelet Activation in Alzheimer’s Disease: From Pathophysiology to Clinical Value
Current Vascular Pharmacology Therapeutic Angiogenesis in Ischemic Heart Disease: Gene or Recombinant Vascular Growth Factor Protein Therapy?
Current Gene Therapy Role of NF-κB in the Regulation of Cytochrome P450 Enzymes
Current Drug Metabolism Prevalence, Correlates and Management of Hyperglycemia in Diabetic Non-critically Ill Patients at a Tertiary Care Center in Lebanon
Current Diabetes Reviews The Electrocardiographic Manifestations of Arrhythmogenic Right Ventricular Dysplasia
Current Cardiology Reviews The COVID-19 Pandemic: A Challenge for the Cardiovascular Health
Current Cardiology Reviews Sigma Receptors and Cocaine Abuse
Current Topics in Medicinal Chemistry Preface [Hot Topic: Cytochrome P450 and Diseases: Implications in Drug Metabolism and Pathophysiology (Guest Editor: Vincent Pichette)]
Current Drug Metabolism IgG4 Related Syndrome: Another Multiorgan Disease in the Interest Field of Internal Medicine
Current Pharmaceutical Design COVID-19 and Diabetes: will Novel Drugs for Diabetes Help in COVID-19?
Current Molecular Pharmacology White Matter Damage Along the Uncinate Fasciculus Contributes to Cognitive Decline in AD and DLB
Current Alzheimer Research The Activating Receptors of Natural Killer Cells and Their Inter-Switching Potentials
Current Drug Targets Astrocytic and Vascular Scaffolding for Neuroblast Migration in the Rostral Migratory Stream
Current Neurovascular Research