Effects of p53-knockout in vascular smooth muscle cells on atherosclerosis in miceReportar como inadecuado




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In vitro and in vivo evidence has indicated that the tumor suppressor, p53, may play a significant role in the regulation of atherosclerotic plaque formation. In vivo studies using global knockout mice models, however, have generated inconclusive results that do not address the roles of p53 in various cell types involved in atherosclerosis. In this study, we have specifically ablated p53 in vascular smooth muscle cells VSMC in the ApoE- mouse model to investigate the roles of p53 in VSMC in atherosclerotic plaque formation and stability. We found that p53 deficiency in VSMC alone did not affect the overall size of atherosclerotic lesions. However, there was a significant increase in the number of p53- VSMC in the fibrous caps of atherosclerotic plaques in the early stages of plaque development. Loss of p53 results in migration of VSMC at a faster rate using wound healing assays and augments PDGF-induced formation of circular dorsal ruffles CDR, known to be involved in cell migration and internalization of surface receptors. Furthermore, aortic VSMC from ApoE-p53- mice produce significantly more podosomes and are more invasive. We conclude that p53- VSMC are enriched in the fibrous caps of lesions at early stages of plaque formation, which is caused in part by an increase in VSMC migration and invasion as shown by p53- VSMC in culture having significantly higher rates of migration and producing more CDRs and invasive podosomes.



Autor: Richard Yang Cao , Robert Eves , Lilly Jia, Colin D. Funk, Zongchao Jia, Alan S. Mak

Fuente: http://plos.srce.hr/



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