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Clonal hematopoiesis is the new cardiovascular risk factor that a team of researchers from the National Center for Cardiovascular Research (CNIC) has identified, as it is a cause of atherosclerosis, according to the Spanish work published in the scientific journal Nature Medicine. In this way, resolve the relationship between clonal hematopoiesis and atherosclerosiswarn of this new risk factor different from the known ones and they go further, as they propose in a second study published in European Heart Journal an ancestral medicine, the colchicineas a personalized strategy to mitigate the effects of clonal hematopoiesis. CNIC researchers have announced the results of both investigations this Friday at the Congress of the European Society of Cardiology held in London (United Kingdom).
Clonal hematopoiesis is the new cardiovascular risk factor that the CNIC has identified as a cause of atherosclerosis
Clonal hematopoiesis is caused by acquired mutations in blood stem cells. It was known that this phenomenon is associated with increased cardiovascular risk, but until now it had not been defined whether it is a cause or consequence of cardiovascular disease. According to the Dr. José Javier Carpenterwho leads the research published in Nature Medicinemost of these mutations are harmless, but “Some of them give the affected cells a competitive advantage that allows them to expand progressively, generating clonal populations of mutant blood cells, a phenomenon known as clonal hematopoiesis.”.
Until now, the scientific community has debated whether somatic mutations linked to clonal hematopoiesis contribute to accelerating the development of atherosclerosis or whether it is the other way around. The CNIC study clarifies the relationship between clonal hematopoiesis and atherosclerosis. For this purpose, a longitudinal study was carried out using data from the PESA-CNIC-Santander study (Progression of Early Subclinical Atherosclerosis). PESA is a prospective study of more than 4,000 apparently healthy middle-aged participants who have been periodically examined with advanced imaging technologies since 2010 to detect the presence and development of atherosclerosis.
It was known that clonal hematopoiesis is associated with a higher cardiovascular risk, but until now it had not been defined whether it is a cause or consequence of cardiovascular disease.
The team used highly sensitive DNA sequencing techniques to detect somatic mutations in blood samples and noninvasive imaging techniques to assess the presence and progression of atherosclerosis. The results of the study are clear: People with mutations linked to clonal hematopoiesis at the beginning of the study were more likely to develop atherosclerosis in the following yearsHowever, the presence or extent of atherosclerosis did not influence the expansion of the mutated blood cells.
“These data indicate that these mutations contribute to the development of atherosclerosis, but are not a consequence of it.”explains Miriam Diez-Diezfirst author of the article. “We cannot rule out, however, that other conditions, such as genetic inheritance or lifestyle, may modulate the effects of clonal hematopoiesis, a possibility that will undoubtedly be examined in the near future.”adds Beatriz L. Ramos-Nebleco-first author.
Research has shown that mutations linked to clonal hematopoiesis contribute to the development of atherosclerosis, but are not a consequence of it.
For researchers, the clinical implications are obvious. Clonal hematopoiesis is a new cardiovascular risk factor, completely different from the traditional risk factors studied in recent decades. This makes it promising for the development of new strategies for the prevention of cardiovascular diseases.
“By demonstrating that mutations linked to clonal hematopoiesis precede and contribute to the development of atherosclerosis, our research suggests that Targeting the effects of these somatic mutations could help prevent cardiovascular disease“José Javier Fuster points out. The second study by the CNIC researchers, published in European Heart Journallays the foundation for this.
For researchers, clonal hematopoiesis is a new cardiovascular risk factor, completely different from the traditional risk factors studied.
Colchicine to prevent the new risk factor
Among the mutations linked to clonal hematopoiesis, the best characterized are those that affect the gene TET2In a 2017 study by José Javier Fuster, published in Sciencemutations in this gene were shown to accelerate the development of atherosclerosis in animal models by causing exacerbated inflammatory responses in the artery wall. Now, in the new study, published in European Heart Journalthe group of José Javier Fuster, in collaboration with Pradeep Natarajan’s groupof the Broad Institute in Boston, proposes that the adverse effects of mutations in TET2 on cardiovascular health could be mitigated with an anti-inflammatory drug, the colchicine.
CNIC researchers co-authored the article published in the European Heart Journal.In studies in animal models, CNIC researchers demonstrated that treatment with colchicine attenuates inflammatory responses and the development of atherosclerosis in animals with mutant cells in TET2making them comparable to that of non-mutant animals. In parallel, the analyses carried out in the Broad Institute They showed that The risk of having a heart attack is attenuated in people with mutations in TET2 treated with colchicine for other diseases.
Researchers propose that the adverse effects of TET2 mutations on cardiovascular health could be mitigated with an anti-inflammatory drug: colchicine
Colchicine is a plant-derived drug found in medicinal plants that has been used for thousands of years in traditional medicine. It is frequently used as an anti-inflammatory in other pathologies such as gout. “The most remarkable thing is that it is a very cheap medicine.accessible in almost the entire world, and already approved to prevent cardiovascular disease by the European Medicines Agency and the American Drug Agency (FDA), which would facilitate its use to prevent cardiovascular risk in people with mutations in TET2″underlines Ms. Angels Zuriagafirst author of the study and responsible for experimental studies at the CNIC.
Researcher José Javier Fuster highlights the importance of the study in the field of personalized medicine, since in clonal hematopoiesis “We found that each mutated gene acts through different mechanisms and, therefore, different interventions are probably required to alleviate its effects”. Therefore, “This study lays the first stone for using colchicine as a personalized treatment in people with TET2 mutations, but new clinical trials will be necessary to demonstrate its efficacy conclusively.”he adds.