Shortness of breath at the slightest effort, cough, fatigue, discomfort… The symptoms of pulmonary arterial hypertension (PAH) resemble those of several heart or lung diseases. In reality, this rare condition is linked to an increase in blood pressure in the arteries that connect the heart to the lungs. It is serious and progresses quickly; lung or cardiopulmonary transplantation still often remains the only option.
To offer the best care and prioritize people in advanced stages for transplantation, “it is important to have biomarkers [soit des molécules] which make it possible to predict the evolution of the disease”, explains the Dr Olivier Boucherat, from the IUCPQ Research Center. Ideally, we would like these markers to provide information on the degree of distress of the heart, which determines the prognosis.
Indeed, in affected people, for complex reasons, the cells of the small blood vessels inside the lungs proliferate, which stiffens their walls and makes blood circulation difficult. Consequence: pressure increases upstream in the pulmonary arteries, and the heart must pump harder to counter the resistance. The right ventricle becomes dangerously tired.
How can we detect the molecule in the blood that would provide instant information on the condition of the heart? Olivier Boucherat and his team have focused on high-throughput omics technologies, which make it possible to obtain a snapshot of the level of thousands of different molecules in a diseased tissue and to compare this portrait to what happens in healthy people.
“We analyzed the hearts of patients who died from this disease to measure the transcriptome and the proteome, that is to say the messenger RNAs and proteins,” explains the researcher. This very broad screening gives a good idea of the signals activated in the suffering tissue. At the same time, the team measured thousands of proteins in the blood of around 200 patients in two different cohorts, then cross-referenced the data.
-Summary: a handful of biomarkers seemed to correlate with the severity of right ventricular damage. In the group, the LTBP2 protein appeared to be a good predictor of the progression of the disease. “It is linked to cardiac fibrosis; a high level in the blood indicates that the heart is very damaged. »
These technologies are still difficult to translate into clinically usable tools, explains Dr.r Boucherat. “A good biomarker should decrease in the blood when patients respond well to the treatment they receive. And to verify this, you need a lot of samples and funding,” he emphasizes.
However, these preliminary results, which were the subject of a publication in Natureshow the full power of “omics” to pinpoint the relevant molecule(s) to guide treatment. “They are a major asset,” believes the specialist. I think that in the future, we will combine several biomarkers to measure, for example, fibrosis, inflammation, stress on cardiac cells and response to treatment. »
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