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
-
The Correspondence Between Magnetic Resonance Images and the Clinical and Intraoperative Status of Patients with Spinal Tumors
Current Medical Imaging Withdrawal Notice: Drug Repurposing for Prospective Anti-Cancer Agents Along with the Clinical Status of the Repurposed Drug
Anti-Cancer Agents in Medicinal Chemistry Time Recall; Future Concept of Chronomodulating Chemotherapy for Cancer
Current Pharmaceutical Biotechnology Inpatient Care of the HIV Infected Patient in the Highly Active Antiretroviral Therapy (HAART) Era
Current HIV Research CXCR4 Receptor as a Promising Target for Oncolytic Drugs
Mini-Reviews in Medicinal Chemistry Determination of Dysregulated miRNA Expression Levels by qRT-PCR after the Application of Usnic Acid to Breast Cancer
Anti-Cancer Agents in Medicinal Chemistry The Effect of Lycopene on the PI3K/Akt Signalling Pathway in Prostate Cancer
Anti-Cancer Agents in Medicinal Chemistry Novel Drugs for Neuroblastoma
Drug Design Reviews - Online (Discontinued) Antiviral Medication in Sexually Transmitted Diseases. Part II: HIV
Mini-Reviews in Medicinal Chemistry Herpes Simplex Virus Type 1 Amplicons and their Hybrid Virus Partners, EBV, AAV, and Retrovirus
Current Gene Therapy Autophagy in Diabetic Retinopathy
Current Neuropharmacology The Molecular Genetics of Lentiviral Vectors - Current and Future Perspectives
Current Gene Therapy The Cancer Preventive Effects of Edible Mushrooms
Anti-Cancer Agents in Medicinal Chemistry Regulatory T Cells and Cancer Therapy: An Old Story with a New Hope
Current Cancer Therapy Reviews Lycorine and its Derivatives for Anticancer Drug Design
Mini-Reviews in Medicinal Chemistry Targeted Toxins for Glioblastoma Multiforme: Pre-Clinical Studies and Clinical Implementation
Anti-Cancer Agents in Medicinal Chemistry Facile Eco-compactable Design for the Synthesis and Characterization of Silver Nanoparticles
Nanoscience & Nanotechnology-Asia Polyphenols Counteract Tumor Cell Chemoresistance Conferred by Multidrug Resistance Proteins
Anti-Cancer Agents in Medicinal Chemistry Patent Selections:
Recent Patents on Anti-Cancer Drug Discovery Deoxypodophyllotoxin Isolated from Juniperus communis Induces Apoptosis in Breast Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry