The Yin and Yang of toll-like receptors in endothelial dysfunction

Endothelial cells (ECs) play a critical role in health and disease due to their widespread distribution and unique location. Although ECs are not regarded as classical immune cells, they actively participate in innate immune and inflammatory responses. EC function is affected by exogenous activators (i.e., infectious agents) and endogenous triggers (i.e., damage-associated molecular pattern molecules (DAMPs) released by stressed or injured cells). Toll-like receptors (TLRs) can recognize both infectious agents and DAMPs and play a key role in activating innate mechanisms in ECs. Endothelial dysfunction (EDF) may lead to tissue damage in various inflammatory and autoimmune diseases through TLRs. This review summarizes the current knowledge about the role of TLRs in a variety of EDF-related conditions, including autoimmunity and graft rejection, cancer, cardiovascular diseases, diabetes and related complications, ischemia and related injuries, and sepsis.