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Contenu archivé le 2022-12-23

Lipoproteins: transmembrane signalling and mitogenic potential in vascular smooth muscle cells

Objectif



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.

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Régime de financement

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Coordinateur

Basel University Hospital
Contribution de l’UE
Aucune donnée
Adresse
Hebelstraße 20
4031 Basel
Suisse

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Coût total
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Participants (2)