Cardiovascular diseases are the leading cause of death in the Western world. They are preferentially due to atherosclerosis, which is characterized by impaired endothelial cell function.

In order to improve vascular function in diseased vessels we have developed a strategy for site-directed gene therapy or endothelial cell replacement by the use of magnetic nanoparticles (MNPs). As a model system we have used an ex vivo flow-loop system and applied a magnetic field in combination with complexes of lentiviral vectors and MNPs. Thereby we obtained a radially symmetric lentiviral transduction of the endothelium for expression of endothelial nitric oxide synthase (eNOS) or vascular endothelial growth factor (VEGF). Similarly, the endothelium of denuded arteries was replaced by MNP-loaded endothelial cells overexpressing functional genes. QRT-PCR and Western Blot analyses revealed a strong elevation of mRNA and protein expression of functional genes in loaded cells and also in vessels after treatment. Enhanced nitric oxide (NO) and VEGF production were demonstrated by measurements with the NO fluorescence indicator DAF-FM or an ELISA, respectively. To determine the effect of radially symmetric eNOS overexpression on vascular tone, isometric force measurements in a myograph were performed and verified elevated basal NO production.

Thus, our strategies using MNPs in combination with magnetic fields for site-directed homogeneous transduction or endothelial cell replacement in vessels allows for an efficient overexpression of functional genes causing improved vascular function. This approach could be helpful to enhance long-term vascular function of grafts for bypass surgery and to directly engineer vessels in vivo.