Objective
Transmembrane signal transduction systems play pivotal regulatory roles in cell metabolism, proliferation, differentiation and function. It is not surprising therefore that aberrant signal transfer responses to vasoactive and growth factors are considered as prime causes in the initiation/progression/maintenance of cardiovascular disease. Blood lipoproteins, as essential regulators of cellular cholesterol homeostasis, are also recognised as substantial contributors to the genesis and progression of cardiovascular diseases such as atherosclerosis and hypertension, although the precise mechanisms of this connection are, to a large extent, unknown.
An important role has been attributed to lipoprotein-induced changes in cellular lipid content. However, evidence is accumulating to suggest that low- and high- density lipoproteins (LDL and HDL) can also influence cellular (in smooth muscle cells, endothelial cells, fibroblasts and platelets) processes which are apparently distinct from those associated with the counter-regulatory roles of LDL and HDL in cholesterol homeostasis. In vascular smooth muscle cells (VSMC), for example, LDL and HDL induce a rapid phosphoinositide catabolic response and several other metabolic responses related to the growth and/or function of these cells. Therefore studies related to hormone or growth factor-like cell signalling properties of lipoproteins will be done. Inositol phosphates are analyzed with HPLC.
While these effects implicate a hormone-like action of lipoproteins, neither the mechanism of action nor the physiological relevance/consequence of lipoprotein-stimulated signal transduction are understood. Investigations will be done to see if the lipoproteins-mediated signalling is receptor-mediated. The spectrum of vascular cell responses to lipoproteins is apparently analogous to those biochemical events elicited by vasoactive peptides and growth factor peptides, and thus lipoproteins exert direct effects on vascular structure and function. Therefore the study of membrane receptors mediating these effects, as well as the study of coupling between these receptors and phospholipase C and Ca2+-channels, will be done due to the potential interest for cardiology, cell biology and pharmacology. The outcome of this project will contribute important information to the knowledge of the role of lipoproteins in modulation of cell growth and hypertrophy, as well as vascular tone and contractility, in both health and cardiovascular disease.
Fields of science (EuroSciVoc)
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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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
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
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Coordinator
4031 Basel
Switzerland
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.