Any inflammatory process, such as trauma, surgery or infection, can cause damage to the endothelial lining of the vessel's wall. The main mechanism is exposure of tissue factor to the blood coagulation system. Inflammatory and other stimuli (such as hypercholesterolemia) can lead to changes in gene expression in endothelium producing to a pro-thrombotic state. When this occurs, endothelial cells downregulate substances such as thrombomodulin, which is a key modulator of thrombin activity. The end result is a sustained activation of thrombin and reduced production of protein C and tissue factor inhibitor, which furthers the pro-thrombotic state.