Key result
Targeting PAR-1 shows potential to modulate angiogenesis in atherosclerosis, restenosis, and cancer.
Why the study?
Angiogenesis plays a critical role in cardiovascular complications and cancer, with thrombin and PAR-1 implicated in its regulation, but therapeutic targeting of PAR-1 requires further understanding.
Does targeting PAR-1 with small-molecule antagonists inhibit angiogenesis in diseases such as atherosclerosis, restenosis, and cancer?
Does targeting PAR-1 with small-molecule antagonists inhibit angiogenesis in diseases such as atherosclerosis, restenosis, and cancer?
Targeting PAR-1 may offer a novel therapeutic approach to inhibit pathological angiogenesis in cardiovascular diseases and cancer.
PAR-1 antagonism remains investigational for angiogenesis-related disease; leaves open whether antagonists will prove clinically effective in atherosclerosis or cancer.
Angiogenesis, the growth of new blood vessels from preexisting ones, is a necessary component of embryogenesis, wound healing, and the proliferative phase of the female reproductive cycle. Angiogenesis also plays a critical role in important pathologic processes such as cancer and cardiovascular complications. In addition, clinical, laboratory, and pharmacologic evidence has shown a link between angiogenesis, coagulation, hemostasis, and thrombosis in the settings of these pathologies. Recent studies in our laboratory revealed that thrombin has a significant stimulatory effect on angiogenesis. This effect of thrombin is independent of fibrin formation and can be attributed mainly to the activation of protease-activated receptor-1 (PAR-1). PAR-1 is widely expressed in vascular cells and is involved in cardiovascular complications such as atherosclerosis, restenosis, and neointimal formation. It is also expressed in many cancer cells contributing to induction of tumor growth and metastasis. In this review, we will summarize our present-day understanding of the role of thrombin and PAR-1 in angiogenesis and the potential therapeutic utility of targeting PAR-1 in angiogenesis-related disease, such as atherosclerosis, restenosis, and cancer.
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Tsopanoglou et al. (2007) conducted a review in Angiogenesis-related diseases (atherosclerosis, restenosis, cancer). Small-molecule antagonists of protease-activated receptor-1 (PAR-1) was evaluated. This review summarizes the role of thrombin and PAR-1 in angiogenesis and the potential therapeutic utility of targeting PAR-1 in diseases such as atherosclerosis, restenosis, and cancer.
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