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
-
Towards the Development of Tumor Necrosis Factor (TNF) Sensitizers:Making TNF Work Against Cancer
Current Pharmaceutical Design Delivery of Intracellular-Acting Biologics in Pro-Apoptotic Therapies
Current Pharmaceutical Design The Biochemical Mechanisms of T-Cell Anergy
Current Immunology Reviews (Discontinued) Application of SMILES Notation Based Optimal Descriptors in Drug Discovery and Design
Current Topics in Medicinal Chemistry PLK1 Inhibition: Prospective Role for the Treatment of Pediatric Tumors
Current Drug Targets Synthesis, Characterization of 4-Anilino-6,7-Dimethoxy Quinazoline Derivatives as Potential Anti-Angiogenic Agents
Anti-Cancer Agents in Medicinal Chemistry Substance Abuse, HIV-1 and Hepatitis
Current HIV Research Focus on MicroRNAs as Biomarker in Pediatric Diseases
Current Pharmaceutical Design Opportunities and Challenges in Nano-structure Mediated Drug Delivery: Where Do We Stand?
Current Nanomedicine Safety Considerations Associated with Development and Clinical Application of Lentiviral Vector Systems for Gene Transfer
Current Genomics Targeting Established Tumor Vasculature: A Novel Approach to Cancer Treatment
Current Cancer Therapy Reviews Chlorophylls and their Derivatives Used in Food Industry and Medicine
Mini-Reviews in Medicinal Chemistry Need to Think Outside Organ-based Diagnosis to Molecular Diagnostics
Applied Clinical Research, Clinical Trials and Regulatory Affairs Targeting CD4 to Disrupt Signaling Through Membrane Rafts: Towards a Raft-Based Therapeutics
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Differentiation Ability of Amniotic Fluid-Derived Stem Cells Cultured on Extracellular Matrix-immobilized Surface
Current Nanoscience Wnt Signaling in Rhabdomyosarcoma – A Potential Targeted Therapy Option
Current Drug Targets The Role of Cytochrome P450 in Cytotoxic Bioactivation: Future Therapeutic Directions
Current Cancer Drug Targets Telomere Maintenance Mechanisms in Cancer: Clinical Implications
Current Pharmaceutical Design Mapping the High Throughput SEREX Technology Screening for Novel Tumor Antigens
Combinatorial Chemistry & High Throughput Screening Recent Advances in PUVA Photochemotherapy and PDT for the Treatment of Cancer
Current Pharmaceutical Design