Abstract
Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by endothelial dysfunction, and in which innate and adaptive immune responses have a crucial role. Autoimmune reactions against several self molecules and modified self molecules have been identified in patients with atherosclerotic disease. Oxidative stress, increasingly reported in these patients is the major event causing protein structural modifications, thus inducing the appearance of neo/cryptic epitopes. Following intraplaque haemorrhage large amounts of cell-free haemoglobin (Hb) accumulate within atheroma, due to its impaired clearance by the haptoglobin-CD163 scavenging system. The pro-oxidative intraplaque microenvironment may induce Hb structural changes, thus generating neo/cryptic autoantigenic epitopes and rendering the oxidized self molecule as a dangerous signal for both immune and endothelial cells. In this review, we will present the most relevant information on Hb as a candidate self antigen involved in the pathogenesis of atherosclerotic disease and on its ability to trigger signals that drive endothelial dysfunction and immune cell activation. On these grounds, we will also discuss how these new paradigms may lead to novel therapeutic targets for cardiovascular diseases.
Keywords: Adaptive immunity, atherosclerosis, CD163, endothelial cells, haptoglobin, innate immunity, oxidized haemoglobin, therapeutic perspectives.
Current Medicinal Chemistry
Title:Oxidized Haemoglobin–Driven Endothelial Dysfunction and Immune Cell Activation: Novel Therapeutic Targets for Atherosclerosis
Volume: 20 Issue: 37
Author(s): Brigitta Buttari, Elisabetta Profumo, Rita Businaro, Luciano Saso, Raffaele Capoano, Bruno Salvati and Rachele Riganò
Affiliation:
Keywords: Adaptive immunity, atherosclerosis, CD163, endothelial cells, haptoglobin, innate immunity, oxidized haemoglobin, therapeutic perspectives.
Abstract: Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by endothelial dysfunction, and in which innate and adaptive immune responses have a crucial role. Autoimmune reactions against several self molecules and modified self molecules have been identified in patients with atherosclerotic disease. Oxidative stress, increasingly reported in these patients is the major event causing protein structural modifications, thus inducing the appearance of neo/cryptic epitopes. Following intraplaque haemorrhage large amounts of cell-free haemoglobin (Hb) accumulate within atheroma, due to its impaired clearance by the haptoglobin-CD163 scavenging system. The pro-oxidative intraplaque microenvironment may induce Hb structural changes, thus generating neo/cryptic autoantigenic epitopes and rendering the oxidized self molecule as a dangerous signal for both immune and endothelial cells. In this review, we will present the most relevant information on Hb as a candidate self antigen involved in the pathogenesis of atherosclerotic disease and on its ability to trigger signals that drive endothelial dysfunction and immune cell activation. On these grounds, we will also discuss how these new paradigms may lead to novel therapeutic targets for cardiovascular diseases.
Export Options
About this article
Cite this article as:
Buttari Brigitta, Profumo Elisabetta, Businaro Rita, Saso Luciano, Capoano Raffaele, Salvati Bruno and Riganò Rachele, Oxidized Haemoglobin–Driven Endothelial Dysfunction and Immune Cell Activation: Novel Therapeutic Targets for Atherosclerosis, Current Medicinal Chemistry 2013; 20 (37) . https://dx.doi.org/10.2174/09298673113209990162
DOI https://dx.doi.org/10.2174/09298673113209990162 |
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
-
Patent Selections
Recent Patents on Biomarkers Role of Immunostimulatory Molecules in Poultry Vaccines
Recent Patents on Biotechnology Targeting DNA Minor Groove by Hybrid Molecules as Anticancer Agents
Current Medicinal Chemistry Synthesis and Application of Stable Nitroxide Free Radicals Fused with Carbocycles and Heterocycles
Current Organic Chemistry The Biology of Neurotrophins, Signalling Pathways, and Functional Peptide Mimetics of Neurotrophins and their Receptors
CNS & Neurological Disorders - Drug Targets Targeting Death Receptors to Fight Cancer: From Biological Rational to Clinical Implementation
Current Medicinal Chemistry Therapeutic Vaccines for Cervical Cancer: Dendritic Cell-Based Immunotherapy
Current Pharmaceutical Design Small and Long Non-Coding RNAs: Novel Targets in Perspective Cancer Therapy
Current Genomics Quantum Dot-Based Nanoprobes for In Vivo Targeted Imaging
Current Molecular Medicine Porphyrins as Radiosensitizing Agents for Solid Neoplasms
Current Pharmaceutical Design Signaling Intermediates (MAPK and PI3K) as Therapeutic Targets in NSCLC
Current Pharmaceutical Design Retroviral Gene Therapy: Safety Issues and Possible Solutions
Current Gene Therapy From TGF-β to Cancer Therapy
Current Drug Targets Biomaterials and Scaffolds in Bone and Musculoskeletal Engineering
Current Stem Cell Research & Therapy Targeting the Atypical Chemokine Receptor ACKR3/CXCR7: Phase 1 - Phage Display Peptide Identification and Characterization
Current Topics in Medicinal Chemistry Redox Regulation and the Autistic Spectrum: Role of Tryptophan Catabolites, Immuno-inflammation, Autoimmunity and the Amygdala
Current Neuropharmacology Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer
Current Medicinal Chemistry Brachytherapy: State of the Art and Possible Improvements
Anti-Cancer Agents in Medicinal Chemistry Flavonoids in Cancer Prevention
Anti-Cancer Agents in Medicinal Chemistry Novel Targets for Apoptosis Modulation: BAG3 Protein and Other Co- Chaperones
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery