Protective role of endothelial p53 in stress induced vascular malignancy.

Accumulation of cellular stress induced mutations has a potential risk for oncogenic transformation. Once the damage is sensed by checkpoint pathway, such as p53, the aberrant cells are immediately eliminated from regular cell cycle system in order to protect life-threatening events. Here, we show endothelial cell (EC)-specific p53 deletion causes spontaneous endothelial tumors with severe hemolytic phenotypes in mice as is the case with hemangioma thrombocytopenia syndrome in human. As a result of the lack of genomic protection by p53, aggravated by oxidative and aging stress induces additional mutation in ECs especially in adipose tissue. This vascular-specific genomic unstability dysregulates the expression of critical genes such as cell cycle signaling leading to aggressive angiosarcomas. Overall design: Expression profiling by high throughput sequencing data; Illumina HiSeq 4000 (Mus musculus).