Endotoxin, Toll-like Receptor-4, and Atherosclerotic Heart Disease
| Autor: | John D. Bowman, Salim Surani, Michael A. Horseman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lipopolysaccharide Heart disease toll-like receptor 4 heart failure Inflammation 030204 cardiovascular system & hematology Article Pathogenesis Sepsis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endotoxin medicine coronary heart disease Toll-like receptor Innate immune system business.industry lipopolysaccharide General Medicine medicine.disease 030104 developmental biology chemistry Immunology TLR4 medicine.symptom atherosclerosis Cardiology and Cardiovascular Medicine business |
| Zdroj: | Current Cardiology Reviews |
| ISSN: | 1875-6557 1573-403X |
| Popis: | Background: Endotoxin is a lipopolysaccharide (LPS) constituent of the outer membrane of most gram negative bacteria. Ubiquitous in the environment, it has been implicated as a cause or con-tributing factor in several disparate disorders from sepsis to heatstroke and Type II diabetes mellitus. Starting at birth, the innate immune system develops cellular defense mechanisms against environmen-tal microbes that are in part modulated through a series of receptors known as toll-like receptors. Endo-toxin, often referred to as LPS, binds to toll-like receptor 4 (TLR4)/ myeloid differentiation protein 2 (MD2) complexes on various tissues including cells of the innate immune system, smooth muscle and endothelial cells of blood vessels including coronary arteries, and adipose tissue. Entry of LPS into the systemic circulation ultimately leads to intracellular transcription of several inflammatory mediators. The subsequent inflammation has been implicated in the development and progression atherosclerosis and subsequent coronary artery disease and heart failure. Objective: The potential roles of endotoxin and TLR4 are reviewed regarding their role in the pathogen-esis of atherosclerotic heart disease. Conclusion: Atherosclerosis is initiated by inflammation in arterial endothelial and subendothelial cells, and inflammatory processes are implicated in its progression to clinical heart disease. Endotoxin and TLR4 play a central role in the inflammatory process, and represent potential targets for therapeutic intervention. Therapy with HMG-CoA inhibitors may reduce the expression of TLR4 on monocytes. Other therapeutic interventions targeting TLR4 expression or function may prove beneficial in athero-sclerotic disease prevention and treatment. |
| Databáze: | OpenAIRE |
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