Abstract
Cardiovascular disease ranks among the leading causes of morbidity and mortality in adult populations in the Western world. Significant progress in understanding the etiology of cardiovascular disease has come from recent recognition that chronic inflammation plays a key role in its development. The principal mediators of this inflammatory response, and the mechanisms by which they work, however, are incompletely understood. Moreover, the complex nature of the inflammatory response poses significant challenges to the development of effective and targeted treatments. Potentially promising targets to reduce inflammation in atherosclerosis include Toll-like receptor (TLR) pathways and anti-inflammatory factors that modulate TLR signaling. In this review, we outline studies that provide insight into the links between cardiovascular disease and inflammation, focusing on innate immunity and endotoxin/TLR4 signaling. We also discuss the contribution of specific host immune/inflammatory responses to atherogenesis, and describe cellular signaling pathways (lipopolysaccharide-binding protein [LBP], CD14, MD-2, TLR4, MyD88, and NF-κB, among others) that play key roles in innate immune signaling. Finally, we discuss the therapeutic potential of modulating these cellular signaling pathways as future strategies for the prevention and treatment of cardiovascular disease, including such approaches as specific targeting of the TLR4 signaling pathway, antibiotic therapy, drug classes with broad anti-inflammatory activity (statins, thiazolidinediones), and the potential of vaccine development. Because of the complexity of the links between low-level chronic infections, inflammation, and atherosclerosis, treatment and prevention of cardiovascular disease will likely require an integrated approach that utilizes a combination of these strategies to target the underlying inflammatory processes.
Keywords: endotoxin, Atherogenesis, CD14 Expression, LPS Binding Protein (LPB), Chemokines, TLR4 Receptor Complex
Current Pharmaceutical Design
Title: Endotoxin, TLR4 Signaling and Vascular Inflammation: Potential Therapeutic Targets in Cardiovascular Disease
Volume: 12 Issue: 32
Author(s): Lynn L. Stoll, Gerene M. Denning and Neal L. Weintraub
Affiliation:
Keywords: endotoxin, Atherogenesis, CD14 Expression, LPS Binding Protein (LPB), Chemokines, TLR4 Receptor Complex
Abstract: Cardiovascular disease ranks among the leading causes of morbidity and mortality in adult populations in the Western world. Significant progress in understanding the etiology of cardiovascular disease has come from recent recognition that chronic inflammation plays a key role in its development. The principal mediators of this inflammatory response, and the mechanisms by which they work, however, are incompletely understood. Moreover, the complex nature of the inflammatory response poses significant challenges to the development of effective and targeted treatments. Potentially promising targets to reduce inflammation in atherosclerosis include Toll-like receptor (TLR) pathways and anti-inflammatory factors that modulate TLR signaling. In this review, we outline studies that provide insight into the links between cardiovascular disease and inflammation, focusing on innate immunity and endotoxin/TLR4 signaling. We also discuss the contribution of specific host immune/inflammatory responses to atherogenesis, and describe cellular signaling pathways (lipopolysaccharide-binding protein [LBP], CD14, MD-2, TLR4, MyD88, and NF-κB, among others) that play key roles in innate immune signaling. Finally, we discuss the therapeutic potential of modulating these cellular signaling pathways as future strategies for the prevention and treatment of cardiovascular disease, including such approaches as specific targeting of the TLR4 signaling pathway, antibiotic therapy, drug classes with broad anti-inflammatory activity (statins, thiazolidinediones), and the potential of vaccine development. Because of the complexity of the links between low-level chronic infections, inflammation, and atherosclerosis, treatment and prevention of cardiovascular disease will likely require an integrated approach that utilizes a combination of these strategies to target the underlying inflammatory processes.
Export Options
About this article
Cite this article as:
Stoll L. Lynn, Denning M. Gerene and Weintraub L. Neal, Endotoxin, TLR4 Signaling and Vascular Inflammation: Potential Therapeutic Targets in Cardiovascular Disease, Current Pharmaceutical Design 2006; 12 (32) . https://dx.doi.org/10.2174/138161206778743501
DOI https://dx.doi.org/10.2174/138161206778743501 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
?Revolutionizing Cancer Treatment: Nano-Therapeutics Targeting Tumor Microenvironment?
This thematic issue explores the forefront of cancer treatment, centering on the groundbreaking potential of nano-therapeutics meticulously designed to target the tumor microenvironment. At its core, the issue aims to unravel the latest advancements in nanotechnology, showcasing innovative materials, formulations, and delivery systems that hold promise for redefining cancer therapeutics. ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...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
-
Psoriasis vulgaris and Psoriasis pustulosa – Epidemiology, Quality of Life, Comorbidities and Treatment
Current Rheumatology Reviews The Co-Existence of NASH and Chronic Kidney Disease Boosts Cardiovascular Risk: Are there any Common Therapeutic Options?
Current Vascular Pharmacology Myocardial Contrast Echocardiography: Role in Clinical Cardiology
Current Vascular Pharmacology Fighting Diabetes: Lessons from Xenotransplantation and Nanomedicine
Current Pharmaceutical Design Medical Management of Parkinsons Disease: Focus on Neuroprotection
Current Neuropharmacology Phenothiazines as Anti-Multi-Drug Resistant Tubercular Agents
Infectious Disorders - Drug Targets Therapeutic Implications of Tocilizumab, A Humanized Anti-Interleukin-6 Receptor Antibody, for Various Immune-Mediated Diseases: An Update Review
Current Rheumatology Reviews Soluble Epoxide Hydrolase, a Target with Multiple Opportunities for Cardiovascular Drug Discovery
Current Topics in Medicinal Chemistry Cellular Cardiomyoplasty – Challenges of a New Era
Current Tissue Engineering (Discontinued) Editorial (Hot Topic: The New Kids on the Block: Oral Direct IIa and Xa Inhibitors Enter the Proscenium of Anticoagulation Treatment)
Current Clinical Pharmacology Anti-Atherosclerotic Therapy Based on Botanicals
Recent Patents on Cardiovascular Drug Discovery Natural Products Based Ayurvedic Formulations: Chemical Cons tituents and Treatment in Neurodegenerative Disordersǂ
Mini-Reviews in Organic Chemistry Genistein Aglycone: A Dual Mode of Action Anti-Osteoporotic Soy Isoflavone Rebalancing Bone Turnover Towards Bone Formation
Current Medicinal Chemistry Prosthetic Valve Endocarditis: Diagnostic Approach and Treatment Options
Cardiovascular & Hematological Disorders-Drug Targets The Relationship between Inflammatory and Oxidative Stress Biomarkers, Atherosclerosis and Rheumatic Diseases
Current Pharmaceutical Design The Circulating Endothelial Cell in Cancer: Towards Marker and Target Identification
Current Pharmaceutical Design From Protein-Protein Interactions to Rational Drug Design: Are Computational Methods Up to the Challenge?
Current Topics in Medicinal Chemistry Biosynthesis and Biological Activities of In Vitro Derived Solasodine Glycoalkaloids from <i>Solanum laciniatum</i>
The Natural Products Journal Catecholamines, Sympathetic Innervation and Immunity: Role in Experimental and Rheumatoid Arthritis
Letters in Drug Design & Discovery Renal Nerve Ablation for Hypertensive Patients with Chronic Kidney Disease
Current Vascular Pharmacology