mutations in the cells of gen p53 are a risk factor in the development of atherosclerotic heart disease. This is demonstrated by a study by the National Center for Cardiovascular ResearchS (CNIC), in collaboration with the American Institutes and published in the journal Nature Heart Research,
This gene encodes a protein known as ‘.seeone of the genomeWhich contributes to maintaining the integrity of the hereditary material of cells, regulating many cellular functions in response to various forms of stress.
An adult person makes hundreds of billions of blood cells every day. This process, although necessary, facilitates event of mutation, In particular, inherited modifications in the p53 gene of these cells increase the risk of developing various types of cancer, including blood cancer.
An adult person makes hundreds of billions of blood cells every day. This process, although necessary, facilitates the appearance of mutations.
group of scientists who lead Jose Javier FesterA CNIC researcher, shows that these mutations also accelerate the development of atherosclerosis, the underlying cause of most heart diseases, first cause of death in the world and one of the largest financial burdens on health care systems.
“We found that carriers of acquired p53 mutations are at increased risk of developing coronary artery disease and peripheral artery disease, completely independent of traditional cardiovascular risk factors, such as high blood pressure or high levels of cholesterol in the blood”, explains Fester.
The mechanisms by which mutations in different genes contribute to cardiovascular disease are different, “which may in the future open the door to personalized cardiovascular disease prevention strategies targeting the specific effects of individual mutations.” nuria matesanzCNIC researcher and co-first author of the article.
in collaboration with groups of derek clarinfrom Stanford University; Pradeep NatarajanMassachusetts General Hospital, and Alexander soldFrom Vanderbilt University, researchers analyzed blood cell sequencing data from more than 50,000 people.
Mice with the p53 mutation developed atherosclerosis due to an abnormally high proliferation of immune cells.
Based on these results, the researchers conducted functional studies in animal models of atherosclerosis in which mutated cells on p53. Mice carrying these mutations developed atherosclerosis in an accelerated manner, mainly because of the abnormally high proliferative immune cells in the wall of the arteries.
“This combination of observations in humans and experimental studies in animals provides strong evidence that these mutations increase the risk of developing heart disease,” says Fuster.
find a novel
Director General of CNIC and one of the authors of the investigation, valentin festerbelieves this work “expands our understanding of the role of acquired mutations in blood cells, a phenomenon called hematopoiesis clonalas a new cardiovascular risk factor”.
Previous studies by the same group showed in an article published in 2021 Journal of the American College of Cardiology (JACC) that many of these mutations, such as those affecting gene TET2Contribute to the development of cardiovascular diseases, among others, atherosclerosis or heart failure.
“Now, in addition to validating these previous findings, we extend them to mutations in the p53 gene and the development of peripheral arterial disease, a disease that is particularly common in the elderly population,” underlines José Javier Fuster .
Matesanj N., et al. «TP53-mutant clonal hematopoiesis accelerates experimental atherosclerosis development». atherosclerosis (2022).