Objective
Hypoxic pulmonary vasoconstriction (HPV) is a unique vasoconstrictor response that diverts blood flow away from poorly ventilated lung regions allowing ventilation-perfusion matching. Despite being a highly conserved adaptive physiological mechanism in lung breathing vertebrates that optimizes blood oxygen saturation, hypoxia sensing in the lung plays a critical pathophysiological role in a number of pulmonary disorders. COPD is associated with chronic hypoxia and can lead in some patients to secondary pulmonary hypertension (PH). Where COPD is confounded with PH, patients have a worse prognosis for survival. In contrast, failure of HPV is often a critical determinant of hypoxemia in sepsis- and trauma-induced lung injury, including the acute respiratory distress syndrome (ARDS). Despite intensive research in the field, the molecular bases of HPV are far from being elucidated. We have recently shown that ceramide production derived from neutral sphingomyelinase (nSMase) and subsequent activation of PKCz are early and necessary events in the signaling cascade of HPV. In sepsis/ARDS an acidic form of SMase is induced. This form can deplete the downstream signaling components of nSMase and is associated with inflammation. Inhibition of nSMase prevents HPV whilst inhibition of aSMase may prevent dysfunction associated with ARDS/sepsis. Thus, these data suggest both nSMase and aSMase are new potential therapeutic targets in the treatment of PH and ARDS/sepsis. The purpose of this application is therefore to fully investigate the role of SMase in the intracellular signaling of hypoxia and inflammation in pulmonary vessels. Secondly, I will investigate associations in SMase activity and gene polymorphisms in tissue from COPD patients with or without PH. This approach will enable us to both identify new treatment targets and potential genetic markers predictive of susceptibility to PH.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2009-RG
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
28040 MADRID
Spain
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.