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Cardiovascular Research Group

 

Projects

Genetics of human cardiovascular disease

 

Porf.dr. Rune Frants

 

Susceptibility genes and metabolic stress.

 

Aim: Delineate the genetics of the metabolic syndrome in human and mouse models.

 

Tools: Patient populations, the diet-sensitive APOE3Leiden mouse model, transcriptomics, metabolomics, and proteomics in a Systems Biology approach.

 

Personnel: Vacanies (Postdoc, AIO, technician)

 

 

Generation and analysis of mouse models

NHS 98.144 to Dr. Erik Biessen and Dr. Ko Willems van Dijk

 

A novel ribozyme based gene therapy for long term reduction of pro-atherogenic lipoproteins.

 

Aim: Development of ribozymes that target genes involved in the production of VLDL (apoB100 and MTP) aimed at down-regulating VLDL production and  thus reduce hyperlipidemia.

 

Tools: Adenovirus mediated gene transfer of ribozymes to the livers of hyperlipidemic mouse models.

 

Personnel: Carlos Vrins (PhD student), Peter van Santbrink (Technician)

 

 

NHS 98.190 to Dr. Ko Willems van Dijk

 

Estrogen receptor alpha mediated gene regulation in the liver and its impact on plasma lipid levels and atherosclerosis.

 

Aim: Delineate the role of estrogens in the modification of gene transcription and subsequent effects on the metabolism of lipoproteins in the liver.

 

Tools: Adenovirus mediated gene transfer of ligand-independent constitutive active or dominant negative forms of the estrogen receptor alpha to the liver of hyperlipidemic mous models.

 

Personnel: Christine d'Oliveira (Post-doc), Andre van der Zee (Technician)

 

 

 

NHS 99.149 to Dr. Ko Willems van Dijk and Dr. Erik Biessen

 

Adenoviral gene delivery to atherosclerotic endothelium to restore endothelial function.

 

Aim: Develop modified adenovirus vectors that preferentially infect vascular endothelial cells. Using these re-targeted adenovirus vectors, genes will be analyzed for their potential to modulate activated endothelial cells that line (pre)atherosclerotic plaques.

 

Tools: Ligands specific for endothelial receptors will be engineered onto the adenovirus vector, either as part of the adenovirus itself or via non-covalent coupling.

 

Personnel: Emile Gras (PhD student)

 

 

 

 

NWO 902.26.220 to Dr. Ko Willems van Dijk

 

The role of estrogen receptor a mediated gene regulation in the vascular

  

Aim: Using modified adenovirus vectors that preferentially infect vascular endothelial cells, the role of estrogen mediated gene regulation will be investigated in the vascular endothelium.

  

Tools: Adenovirus mediated gene transfer of ligand-independent constitutive active or dominant negative forms of the estrogen receptor alpha to the vascular endothelium of hyperlipidemic mous models.

 

Personnel: Yvonne Krom (PhD student)

 

 

 

NHS 2000.099 to Prof. Louis Havekes and Dr. Ko Willems van Dijk

 

In vivo structure-function analysis of apoE to delineate the functional domains that modulate the metabolism of VLDL.

 

Aim: Dissect the role of specific domains of apoE in the various processes that are affected by apoE.

 

Tools: Adenovirus mediated gene transfer of mutated forms of apoE to Apoe-deficient mice.

 

Personnel: Gery Gerritsen (PhD student)

 

 

 

NHS 2001.141 to Dr. Ko Willems van Dijk

 

Molecular mechanims and pathways underlying the effects of estrogens on lipid metabolism.

 

Aim: Delineate the role of estrogens in the modification of gene transcription and subsequent effects on the metabolism of lipoproteins in the liver. Follow-up of project NHS 98.190

 

Tools: Adenovirus mediated gene transfer of ligand-independent constitutive active or dominant negative forms of the estrogen receptor alpha to the liver of hyperlipidemic mous models.

 

Personnel: Vacancy (post-doc)

 

 

 

Dr. Ko Willems van Dijk

 

Peripheral tissues and metabolic stress

 

Aim: Delineate the mechanism of high fat feeding on the development of the metabolic syndrome.

 

Tools: The diet-sensitive APOE3Leiden mouse model, transcriptomics, metabolomics, and proteomics in a Systems Biology approach.

 

Personnel: Vacancy (AIO)

 

 

Novel gene discovery using mouse models