Thrombin receptor expression in normal and atherosclerotic human arteries.

Abstract

Thrombin is a multifunctional serine protease generated at sites of vascular injury. A host of thrombin actions on vascular endothelial cells, smooth muscle cells, and macrophages has been defined in cell culture systems, but the in vivo significance of these activities is unknown. We have defined the expression of the recently identified receptor for thrombin in human arteries by both in situ hybridization and immunohistochemistry. In normal-appearing arteries, thrombin receptor was expressed almost exclusively in the endothelial layer. By contrast, in human atheroma, the receptor was widely expressed, both in regions rich in macrophages and in regions rich in vascular

Increased Expression of Matrix Metalloproteinase-1 in Systemic Vessels of Preeclamptic Women

“…33 Although overexpression of PAR-1 in the preeclamptic placenta has been previously demonstrated, 35 we show herein, for the first time to our knowledge, that PAR-1 expression is increased in the vasculature of women with preeclampsia. Because PAR-1 is mostly confined to the endothelium in healthy human arteries, whereas during an inflammatory process, its expression is enhanced in regions associated with leukocyte influx, 57 it is logical to infer that the increase in vascular PAR-1 during preeclampsia is mediated by infiltrating neutrophils. Contact between infiltrating neutrophils and VSMCs could induce overexpression of PAR-1, which then may be activated by the MMP-1 present in the microenvironment, triggering a cascade of downstream events that result in vascular dysfunction in women with preeclampsia.…”

Up‐regulation of proteinase‐activated receptor 1 and increased contractile responses to thrombin after subarachnoid haemorrhage

“…However, the expression of PAR 1 in smooth muscle has been shown to be upregulated in vascular lesions such as those seen in atherosclerosis (Nelken et al, 1992;Ku and Dai, 1997) and balloon injury models (Wilcox et al, 1994;Fukunaga et al, 2006). Such upregulation of PAR 1 expression in smooth muscle is thus considered to play a critical step in the development of vascular lesions and hyper-contractile state (Hirano, 2007).…”

Protease activation of calcium-independent phospholipase A2 leads to neutrophil recruitment to coronary artery endothelial cells

“…Thrombin generated at sites of vascular injury is the most potent activator of blood platelets [7,8] and its action on inflammatory cells has been well characterized, serving as a chemotactic agent for monocytes [9] and a mitogenic for both lymphocytes [10] and vascular smooth muscle cells [11,12]. Thrombin activation of the vascular endothelium occurring in response to vascular injury or wounding can be beneficial in the repair process, but has the potential to mediate a prolonged inflammatory response and proliferative cellular events in the blood vessel wall, such as those that occur in atherosclerosis and restenosis [13]. Similarly, increased numbers of degranulated mast cells have been found in the adventitia of infarct-related coronary arteries [14] and the mediators released from these granules, including tryptase, are mitogens and co-mitogens for human fibroblasts, stimulating collagen synthesis [15].…”