Toll-like receptor 7 regulates cardiovascular diseases.

Abstract

Cardiovascular disease (CVD) is the major leading cause of morbidity and mortality worldwide. According to the pro-inflammatory nature of CVD, recent studies highlighted the immune system's role in its pathogenesis and development. Toll-like receptors (TLRs) have been identified as dominant innate immune receptors. TLR-7 is an intracellular receptor expressed on endosomes or cytoplasmic reticulum and is responsible for detecting damage-associated molecular patterns, which are remarkable during inflammation and viral infection. In addition to immune cells, TLR-7 is expressed in endothelial cells, vascular smooth muscle cells, and platelets. TLR-7 ligands are single-stranded ribonucleic acid (ssRNA) and short interfering RNA, which can activate the signaling pathway and lead to both inflammatory (e.g., interleukin-1 (IL-1), IL-6, IL-12, tumor necrosis factor- α (TNF-α)) and anti-inflammatory (e.g., IL-10) cytokines release. By growing evidence, it has been proven that TLR-7 activated platelets can increase the risk of thrombus formation by neutrophil aggregation. At the same time, they have a protective role against thrombosis by releasing granulocyte-macrophage colony-stimulating factors. The same two-sided effect was observed between TLR-7 and atherosclerotic plaque formation. Moreover, recent studies explained an association between TLR-7 activation and increased risk of complete heart block, myocarditis, left ventricular remodeling, and rupture. Here we review the rapid progress that has been made in this field, which has improved our understanding of TLR-7 function in CVDs, and discuss the current treatments targeting this receptor.