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SFB: Biomembranes: Molecular Mechanisms of Diabetes-induced Vascular Dysfunction
Subproject of: SFB: Biomembranes: Molecular Aspects of Ion Channels
- Abstract
- Contribution of glycated low-density lipoprotein to changes in subcellular Ca2+ signaling, vasoactivity and gene expression of smooth muscle cells in diabetes mellitus and hypercholesterolemia
Hypercholesterolemia (HC) and diabetes mellitus (DM) are associated with vascular dysfunction and atherosclerosis.
Although these vascular complications have different anthologies in DM and HC, elevated plasma glycated LDL (gLDL) levels are strikingly similar in the two diseases.
In this project, gLDL will be investigated as a link between DM and HC in atherosclerosis.
In our previous work, an increased contractility was found in arteries derived from patients with HC and DM. This correlated with a perturbation of subcellular Ca2+ distribution in freshly dispersed smc from these arteries.
Since subcellular Ca2+ distribution is controlled primarily by the sarcoplasmic reticulum, the nuclear envelop and the mitochondria, the architectural organization of these Ca2+ stores is crucial to the effective control of cytosolic Ca2+.
Therefore we intend to investigate
the architectural remodeling of the cell organelles to be critical to the perturbations of subcellular Ca2+ handling and to the development of cell dysfunction that occurs in HC and DM and
changes in subcellular Ca2+ distribution to affect the patterns of gene expression resulting in pathological variations of protein expression favoring the genesis of vascular complications in HC and DM.
We expect that this work will discover early steps in the development of vascular complications in HC and DM. This might lead the design of novel therapies aimed at preventing the development of vascular complications in HC and DM.
- Project Leader:
- Graier Wolfgang
- Duration:
- 01.10.2001-30.09.2005
- Programme:
- Spezialforschungsbereiche (SFB)
- MUG Research Units
- Division of Molecular Biology and Biochemistry