Thrombin is clearly a key trigger of thrombosis, the proximal cause of most morbidity and mortality in atherosclerotic cardiovascular disease. Might thrombin also contribute to longer-term, structural changes in the arterial wall that promote narrowing and clotting? A study in this issue of the JCI argues that it can. Aihara et al. report that haploinsufficiency of heparin cofactor II, a glycosaminoglycan-dependent thrombin inhibitor, exacerbates injury- or hyperlipidemia-induced arterial lesion formation in mice, possibly by excessive thrombin signaling through protease-activated receptors (see the related article beginning on page 1514).
Eric Camerer
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