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The Role of Toll-like Receptors in Atherothrombotic Cardiovascular Disease

Journal

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
Volume 3, Issue 3, Pages 457-471

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsptsci.9b00100

Keywords

TLR; cytokines; inflammation; atherosclerosis; thrombosis

Funding

  1. National Health and Medical Research Council of Australia [1022800]
  2. National Heart Foundation of Australia [G09M4385]
  3. Diabetes Australia Research Trust
  4. University of Queensland
  5. NHMRC-Peter Doherty [1160925]
  6. National Heart Foundation [102129, 102761]
  7. American Heart Association [18CDA34110359]
  8. National Health and Medical Research Council of Australia [1160925] Funding Source: NHMRC

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Toll-like receptors (TLRs) are dominant components of the innate immune system. Activated by both pathogen-associated molecular patterns and damage-associated molecular patterns, TLRs underpin the pathology of numerous inflammation related diseases that include not only immune diseases, but also cardiovascular disease (CVD), diabetes, obesity, and cancers. Growing evidence has demonstrated that TLRs are involved in multiple cardiovascular pathophysiologies, such as atherosclerosis and hypertension. Specifically, a trial called the Canakinumab Anti-inflammatory Thrombosis Outcomes Study showed the use of an antibody that neutralizes interleukin-1 beta, reduces the recurrence of cardiovascular events, demonstrating inflammation as a therapeutic target and also the research value of targeting the TLR system in CVD. In this review, we provide an update of the interplay between TLR signaling, inflammatory mediators, and atherothrombosis, with an aim to identify new therapeutic targets for atherothrombotic CVD.

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