Título completo

PI20/01363 ISCIII-ROLE OF THE IL-11 SYSTEM IN PULMONARY ARTERIAL HYPERTENSION AND PULMONARYHYPERTENSION ASSOCIATED TO CHRONIC RESPIRATORY DISEASES

Descripción

Idiopathic pulmonary arterial hypertension (PAH) (class 1) and pulmonary hypertension (PH) associated to chronic lung diseases (CLD) such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) (group 3) are severe vascular diseases with an elevated mortality. Recent evidence indicate that IL-11 system could be involved in PAH and PHCLD. Previous findings of our group indicate an overexpression of IL-11 in pulmonary arteries (PA) from idiopathic PAH
and PHCLD-IPF. Furthermore, IL-11 has the potential to induce cell proliferation, migration, inflammation and fibrosis that are also observed in PH.
In this project, members of the IL-11 system, together with molecular markers of PA remodeling, will be measured in lung tissue, isolated PA and serum of patients with PAH, PHCLD (IPF-COPD) and control-healthy subjects, and correlated with disease clinical parameters of severity, to evaluate the role of IL-11 system as biomarker of PH. In isolated human PA (ex vivo) it will be tested the effect of IL-11 system on PA vasoconstriction in organ baths and precision cut lung slice 3D videomicroscopy. In other experiments, it would be evaluated, in vitro, the role of the IL-11 system on primary human PA endothelial and smooth muscle cells, PA stromal fibroblasts, circulating fibrocytes and monocytes, on a broad of cellular processes involved in PH and PA remodeling. In addition, It will be analyzed the direct effect of IL-11 on PH through the chronic IL-11 administration. Different animal models of monocrotalin, bleomycin and cigarette smoke-induced PH will be evaluated under the administration of therapeutic siRNA-IL-11/IL-11R. The results obtained in this pre-clinical and translational study can be of potential value to future clinical strategies and treatments in PAH and PHCLD patients.
The main objective of this research project is to evaluate the participation of the IL-11 system in the activation and cellular transformations that participate in idiopathic PAH and HPCLD such as IPF and COPD, as well as in the clinical and functional characteristic aspects as preclinical and translational basis of futures treatments.

Referencia/Expediente

PI20/01363

Directora

JAVIER MILARA PAYÁ

Fecha de comienzo

1/1/2021

Duración

3 años

Organismo Financiador

INSTITUTO DE SALUD CARLOS III

Naturaleza

NACIONAL

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