Translational research in pulmonary vascular diseases: cell proliferation and apoptotic mechanisms in pulmonary arterial hypertension

Problem

Pulmonary hypertension (PH) is a disease in which the blood pressure of the pulmonary arteries is abnormally high. It usually develops in association with pulmonary artery diseases, and also as a complication in more common lung and heart diseases.

The most significant clinical repercussion of PH is that it gives rise to an overload in the right ventricle, causing this to fail and resulting in death.

It is important to correctly diagnose and describe the mechanism that produces PH, as its treatment varies, depending on the type of hypertension.

Today, different drugs are available that offer enormous benefits to patients with pulmonary hypertension, but it is not yet possible to say that a cure exists for this disease. The group’s goal is to gain deeper knowledge of the mechanisms responsible for PH and to find new activity biomarkers of the disease and new therapeutic lines to correct the underlying problem.

Approach

Pulmonary arterial hypertension is a disease of the small pulmonary arteries in which blood vessel diameter is gradually reduced due to an increase in the thickness of the vessel walls (vasoconstriction). This leads to an increase in pulmonary vascular resistance (PVR) which causes right ventricular failure and death.

Recent therapeutic advances have managed to increase survival and improve the quality of life of patients with PH, but the drugs available today are unable to alter the progression of the disease and the structural lesions of the pulmonary arteries, acting simply as vasodilators.

In the group’s opinion, in addition to vasodilators, it is necessary to find new signalling pathways that could be more appropriate therapeutic targets. In this respect, it is proposed to not only work in the laboratory with animal and cell models, but also to work with blood and tissue samples from patients undergoing lung transplants.

The group’s line of research consists of evaluating potential therapeutic targets and biomarkers of disease activity and progression, aimed at reversing the proliferative remodelling phenotype in PH.

Impact

Molecular study and clinical repercussions of pulmonary arterial hypertension and chronic pulmonary thromboembolic disease.

A pulmonary artery hypertension model has been set up in rodents consisting of exposure to hypoxia related to the administration of a VEGF inhibitor. This model reproduces the disease and identifies new potential therapeutic targets, in order to reverse the pro-proliferative and anti-apoptotic phenotype.

Various members of the group belong to the functional pulmonary hypertension unit at the Hospital Clínic, the most active unit in Catalonia and the second most active in Spain. The unit is accredited as an Expert Referral Unit by the Catalan Health Service (CatSalut), as a CSUR (referral centres, services and units) by the Spanish Ministry of Health and as a healthcare provider of the European Reference Network on Rare Lung Diseases (ERN-LUNG), established by the European Commission, thus increasing its capacity to take on translational research projects and participate in international clinical trials.