Toll-Like Receptors in Angiogenesis

Abstract

Toll-like receptors (TLRs) are known as pattern-recognition receptors related to the Toll protein of Drosophila. After recognition of pathogen-associated molecular patterns of microbial origin, the TLRs alert the immune system, and initiate innate and adaptive immune responses. The TLR system, though, is not confined solely to the leukocytemediated immune defense against exogenous pathogens. Besides myeloid cells, TLR expression has been reported in multiple tissues and cell types, including epithelial and endothelial cells. Moreover, despite the microbial patterns that are commonly accepted as TLR ligands, there is increasing evidence that TLRs also recognize host-derived molecules. In this regard, recent studies point to an involvement of TLRs in various chronic inflammatory disorders and cardiovascular diseases, including atherosclerosis, rheumatoid arthritis, systemic lupus erythematosus, and even cancer. A common feature of these disorders is an enhanced so-called inflammation-induced angiogenesis. However, inflammation-induced angiogenesis is not solely a key component of pathogen defense during acute infection or chronic inflammatory disorders, but also plays a critical role in repair mechanisms, e.g., wound healing and subsequent tissue regeneration. Interestingly, the latest research could coincidentally demonstrate that TLR activation promotes angiogenesis in various inflammatory settings in response to both exogenous and endogenous ligands, although the precise mode of action of TLRs in this context still remains ambiguous. The objective of this review is to present evidence for the implication of TLRs in angiogenesis during physiological and pathophysiological processes, and the potential clinical relevance for new treatment regimes involving TLR modulation.

Deficiency of Nucleotide-binding oligomerization domain-containing proteins (NOD) 1 and 2 reduces atherosclerosis

“…Later identified endogenous ligands for PRRs, such as degradation products of extracellular matrix components released during tissue damage or apoptotic cell material, rather than live pathogens seem to be responsible for PRR-dependent effects in atherosclerosis. Different to NOD receptors, endogenous ligands for almost every member of the TLR family have been described [14]. Moreover, dietary unsaturated fatty acids such as lauric acid (dodecanoic acid) from coconut oil have been shown to activate TLR4 [31] as well as NOD1 and NOD2 [34], demonstrating a potential influence of PRRs on In the current study, we detected an effect of Nod1/2-deficiency on experimental atherosclerosis and lipid metabolism, whereas we did not observe effects on insulin resistance.…”

Anti‐angiogenesis effect of β‐D‐mannuronic acid (M2000) as a novel NSAID with immunosuppressive properties under experimental model

“…Therefore, it is the microenvironment condition of the tissue that determines angiogenic switch and the extent of neovascularization under both physiologic and pathologic conditions. In addition, today there is even strong evidence regarding the role of toll‐like receptors (TLRs) in the angiogenesis process (though their role in developmental angiogenesis is completely unknown) . Thus, further studies are required to determine the mechanism (s) through which M2000 exerts its anti‐angiogenic properties.…”