Pulmonary Hypertension

Coordinator: Dr. Joan Albert Barberà Mir

New markers and therapeutic targets for the diagnosis and treatment of pulmonary hypertension. 

Pulmonary hypertension is a hemodynamic disorder that may originate from a primary alteration of the pulmonary vessels or develop as a complication of other pulmonary or left heart diseases. Progression of PH results in right ventricular (RV) impairment that may progress to RV failure and death. PH is currently classified into 5 groups: 1) pulmonary arterial hypertension (PAH), 2) PH due to left heart disease, 3) PH due to lung diseases and/or hypoxia, 4) chronic thromboembolic pulmonary hypertension (CTEPH), and 5) PH with unclear or multifactorial mechanisms.

PAH and CTEPH are disorders affecting primarily the pulmonary vessels. Both have reduced prevalence (15 and 3 cases per million population, respectively) fulfilling the criteria for rare diseases. They are also severe diseases with poor prognosis if they are not adequately treated PAH affects medium age individuals with a mean survival of less than 3 years if the disease is not treated with new targeted therapies. CTEPH may develop in up to 3.8% of patients suffering an acute pulmonary embolism and has 50% mortality in the first year if not treated with pulmonary endarterectomy or targeted therapy.

PH may also develop in patients suffering respiratory diseases (COPD, interstitial lung diseases, respiratory failure) or left heart diseases. These secondary forms of PH are highly prevalent. For instance, more than 50% of patients with advanced COPD and 40% of patients with advanced pulmonary fibrosis may show PH. In respiratory diseases the presence of PH is associated with poorer outcomes –survival, exacerbations– and increased use of health resources.

In summary, PH is a severe condition causing significant burden. Fortunately, recent advances in the understanding of the pathobiology of PH have prompted the development of new drugs that have provided significant benefit, both in terms of survival and patient’s well-being, particularly in PAH.

Nevertheless, we are far from an optimal situation, given the fact that affected patients are relatively young and current survival in newly diagnosed cases has only raised to 65% at 3 years after diagnosis. There is still a long way to go before we can get a cure of the disease.

Therefore, there is an urgent need to find new therapeutic approaches and diagnostic tools to detect the disease earlier, accurately monitor its progression and treat it more efficiently. Furthermore, secondary forms of PH, in particular those associated with respiratory diseases, represent a major health problem because of its high prevalence, adverse prognostic implications and lack of adequate treatment.

The current project of the PH line at CIBERES addresses these major needs undertaking a comprehensive approach that covers the diverse clinical forms of the disease, taking advantage of common pathophysiological mechanisms underlying the different forms of presentation.

Overall, the multidisciplinary nature of the CIBERES PH research line provides a unique opportunity to address the current key questions in the major clinical forms of PH. The aim of the research project is to identify new activity markers, signals and therapeutic targets for PH, with the ultimate goal to contribute to alleviate and cure the disease.

Objectives

To achieve this ambitious goal the line plans to develop a comprehensive set of investigations addressed to achieve the following major objectives :

  1. Identify novel biomarkers and candidate therapeutic targets using “omics “ sciences.
  2. Analyse the role of new imaging techniques in the early diagnosis of pulmonary vascular remodelling, the assessment of metabolic changes associated with cell growth, the structure and function of the RV and the cardio-vascular coupling.
  3. Evaluate the role of circulating elements (progenitor cells, microparticles) and epigenetic changes in the pathogenesis of PH and their potential as disease biomarkers.
  4. Investigate innovative pharmacological approaches targeting new signalling pathways.
  5. Identify common pathways between pulmonary arterial hypertension and PH associated with respiratory diseases or hypoxia, and investigate innovative treatments that do not impair gas exchange.
  6. Identify the pathophysiological mechanisms that contribute to the lack of thrombus resolution and the development of peripheral vasculopathy in CTEPH.