OBJECTIVE: It has been suggested that deregulated expression of the tumor suppressor protein p53 may play a role in the pathogenesis of occlusive vascular remodeling. However, the role of p53 in cell proliferation and apoptosis in vascular lesions has been controversial. METHODS AND RESULTS: We tested the potential involvement of p53-mediated molecular signaling in lesion formation using a mouse model of vascular injury that may resemble balloon angioplasty. A large wire was inserted into the femoral artery of p53+/+ and p53-/- mice. There was no significant difference in the occurrence of rapid-onset apoptosis, that is, 4 hours after injury. At 2 weeks, the number of proliferating cells in the lesion of p53-/- mice was significantly higher than that observed in p53+/+ mice. The frequency of apoptotic cells was significantly lower in p53-/- mice than in p53+/+ mice. At 4 weeks, the neointimal hyperplasia of p53-/- mice was greater than that of p53+/+ mice. There was no significant difference in the frequency of apoptosis in the lesions. CONCLUSIONS: These results indicate a crucial role of p53 in pathological vascular remodeling after mechanical injury and provide the basis for the development of new therapies targeting p53 for a prophylactic treatment of vascular diseases.
OBJECTIVE: It has been suggested that deregulated expression of the tumor suppressor protein p53 may play a role in the pathogenesis of occlusive vascular remodeling. However, the role of p53 in cell proliferation and apoptosis in vascular lesions has been controversial. METHODS AND RESULTS: We tested the potential involvement of p53-mediated molecular signaling in lesion formation using a mouse model of vascular injury that may resemble balloon angioplasty. A large wire was inserted into the femoral artery of p53+/+ and p53-/- mice. There was no significant difference in the occurrence of rapid-onset apoptosis, that is, 4 hours after injury. At 2 weeks, the number of proliferating cells in the lesion of p53-/- mice was significantly higher than that observed in p53+/+ mice. The frequency of apoptotic cells was significantly lower in p53-/- mice than in p53+/+ mice. At 4 weeks, the neointimal hyperplasia of p53-/- mice was greater than that of p53+/+ mice. There was no significant difference in the frequency of apoptosis in the lesions. CONCLUSIONS: These results indicate a crucial role of p53 in pathological vascular remodeling after mechanical injury and provide the basis for the development of new therapies targeting p53 for a prophylactic treatment of vascular diseases.
Authors: Subhradip Mukhopadhyay; Toni M Antalis; Khanh P Nguyen; Mark H Hoofnagle; Rajabrata Sarkar Journal: Blood Date: 2017-03-20 Impact factor: 22.113