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Toll-Like Receptors: Link between “Danger” Ligands and Plaque Instability

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Abstract:

Myocardial infarction and stroke are exaggerated by rupture of atherosclerotic lesions. Rupture-sensitive plaques have a specific composition which renders them vulnerable, but additional factors (acute infection, higher sympathetic activity, excessive increase of blood pressure or exposure to a variety of drugs) are needed to set off the event. Toll-like receptors are important components of the innate and adaptive immune system and seem to be a potential link between inflammation, infectious disease and atherosclerosis. In addition to classical bacterial and viral antigens, several endogenous ligands (HSP, ox-LDL, apoptotic cells) have also been proposed to react to TLRs. There is accumulating evidence substantiating the contribution of the TLR-signaling pathway not only in the initiation but also in the progression of atherosclerosis. TLRs also play a key role in the development of tissue ischemia. Apoptosis and inflammation comprise two important indicators of plaque instability, and trigger factors augmenting rapidly TLR signaling can lead to aggravation of plaque-rupture.

Due to their multiplex involvement in ischemic conditions, Toll-like receptors may be a promising target for therapeutic intervention. In situations such as acute coronary syndrome, in which inhibition of the inflammatory cascade is warranted, the administration of TLR-blocking agents as adjuvant therapy and the clinical usefulness of this association should be considered.



Document Type: Research Article

Publication date: 2009-06-01

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  • Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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