Unchecked thrombin is bad news for troubled arteries
J. Clin. Invest. Eric Camerer, et al. 117:1486 doi:10.1172/JCI32473 [Go to this article.]

Figure 2
How might HCII deficiency exacerbate responses to arterial injury? Arterial injury may trigger thrombin formation by exposing extravascular TF to circulating coagulation zymogens (see Figure 1). Thrombin activates platelets and converts fibrinogen to fibrin, thus triggering thrombosis and thus, potentially, acute vascular occlusion. Both thrombin and upstream proteases VIIa and Xa may also contribute long-term to arterial remodeling and narrowing (stenosis) by signaling to circulating and mural cells through PARs. At least in vitro, PAR activation triggers leukocyte chemotaxis, endothelial contraction/secretion/expression of adhesion molecules, and smooth muscle cell proliferation/migration. The thrombin inhibitor HCII may be uniquely suited to inhibiting thrombin in the vessel wall, since it is activated by DS, which is synthesized by smooth muscle cells and fibroblasts. AT, by contrast, is only activated by HS enriched in the subendothelial matrix. Tissue-specific thrombin inhibition may thus explain why even partial loss of HCII activity exacerbates arterial remodeling in response to injury or hyperlipidemia in mice, as shown by Aihara et al. in this issue of the JCI (14). m, mice; h, humans.