Co-expression of p53 and MDM2 in human atherosclerosis: implications for the regulation of cellularity of atherosclerotic lesions

p53-Dependent ICAM-1 overexpression in senescent human cells identified in atherosclerotic lesions

“…10 Although the absence of p53 accelerates atherosclerosis by increasing cell proliferation in apoE-knockout mice, 44 it has been shown that wild-type p53 accumulates in human atherosclerotic tissues. 33,45 Moreover, and in agreement with the results presented here ( Figure 5, Table 1), it has been reported that the majority of these p53 immunoreactive cells express p21 WAF1 . 45 These cells are not proliferating, while only few of them exhibit 33,45 The above, in conjunction with our previous observation that ICAM-1 can be induced by p53, 19 suggest a mechanism for the direct involvement of p53 in atherogenesis.…”

“…Interestingly, in semiserial sections we also observed increased p53 accumulation within the nuclei of foam cells, as previously reported. 33 The enhanced expression of MDM2, a classical p53-target protein, in the same nuclei strongly suggests that p53 is transcriptionally active in these cells (Table 1). A similar expression pattern was obtained for the p53-target gene p21 WAF1 , the latter being also a 'hallmark' of cellular senescence.…”

Rhythm changes of clock genes, apoptosis-related genes and atherosclerosis-related genes in apolipoprotein E knockout mice

“…The tumour suppressor protein p53, is involved in both cell proliferation and apoptosis, and is upregulated by various inducers of cellular stress known to be present in an atheromatous setting (27). p53 expression is increased in human atherosclerotic lesions, both in lipid-laden macrophages and smooth muscle cells (28). Vascular smooth muscle cells isolated from atherosclerotic plaques are more susceptible to p53-mediated apoptosis than normal vascular smooth muscle cells (29).…”

Induction of Atherosclerotic Plaque Rupture in Apolipoprotein E −/− Mice After Adenovirus-Mediated Transfer of p53

“…13 p53 expression is increased in human atherosclerotic lesions, both in lipid-laden macrophages and vascular smooth muscle cells. 9,10 Interestingly, vascular smooth muscle cells (VSMCs) isolated from atherosclerotic plaques are more susceptible to p53-mediated apoptosis than normal VSMCs. 14, 15 Guevara et al 16 have demonstrated that atherosclerosis is aggravated in p53/apolipoprotein E (ApoE) double-knockout (p53 Ϫ/Ϫ /ApoE Ϫ/Ϫ ) mice through an increase in p53-controlled proliferation.…”