Toll-like receptor-linked signal transduction in angiogenesis

Abstract

Mammalian Toll-like receptors (TLRs) represent pattern recognition receptors of the immune system and are related to the Toll protein of Drosophila. Pathogen-associated molecular patterns (PAMPs) of microbial and viral origin bind to TLRs and initiate the innate and adaptive immune response. However, TLRs are not solely found on cells of the immune system but also on nonmyeloid cells in various tissues, e.g., on vascular cells. In addition to PAMPs, there is increasing evidence that TLRs also recognize endogenous ligands. Recent studies demonstrate the contribution of distinct TLRs in different inflammatory disorders such as cardiovascular diseases, rheumatoid arthritis, systemic lupus erythematosus, and cancer. Many of these disorders are characterized by enhanced angiogenesis which is mainly trigged by inflammation. However, this inflammation-induced angiogenesis is not only important for pathogen defense during acute infection or chronic inflammatory disorders but as well involved in regenerative processes during wound healing and tissue repair. There is cumulative evidence that TLR activation by exogenous as well as endogenous ligands especially contributes to angiogenic process in this scenario. The present chapter will summarize the current understanding of TLR- linked signal transduction in angiogenesis during inflammatory processes with future prospects for pro- or antiangiogenic therapy.