The absence of p53 accelerates atherosclerosis by increasing cell proliferation in vivo

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Abstract
The tumor suppressor protein p53 is an essential molecule in cell proliferation and programmed cell death (apoptosis), and has been postulated to play a principal part in the development of atherosclerosis. We have examined the effect of p53 inactivation on atherogenesis in apoE-knockout mice, an animal model for atherosclerosis1,2. We found that, compared with p53+/+/apoE–/– mice, p53–/–/apoE–/– mice developed considerably accelerated aortic atherosclerosis in the presence of a similar serum cholesterol in response to a high-fat diet. Furthermore, the atherosclerotic lesions in p53–/–/apoE–/– mice had a significant (~280%) increase in cell proliferation rate and an insignificant (~180%) increase in apoptosis compared with those in p53+/+/apoE–/– mice. Our observations indicate that the role of p53 in atherosclerotic lesion development might be associated with its function in cell replication control, and that p53-independent mechanisms can mediate the apoptotic response in atherosclerosis.