Modulation of gene expression as therapy for atherosclerosis

Atherosclerosis-related cardiovascular disorders continue to be the major cause of morbidity and mortality in Western society. In particular, the acute complications of atherosclerosis are a major burden for health care as adequate therapies are not available. A major research line within the Division of Biophannaceutics of the Leiden/Amsterdam Center for Drug Research involves the design and evaluation of preventive (gene) therapies in this respect. To this end, advanced animal models for atherosclerosis hate been generated curd proof-of-concept studies Mare been performed for improving the pathophysiology of atherosclerotic lesions in the afore-mentioned animal models. Moreover, safe and effective non-viral gene transfer protocols are currently being developed, which are more appropriate in a clinical setting. In this paper we present an overview of our research activities toward targeted (gene) therapy for atherosclerosis. The generation of a unique mode I for vulnerable lesions with a high incidence of thrombotic complications will be described, (is trill its successful application as a testing ground for (adenoviral) plaque stabilizing therapies. Because viral gene therapy vectors pose the risk of adverse side effects, the shall, in this review, also elaborate on the potential of tissue-targeted gene vectors that core equipped with homing devices for the aimed tissue, and of non-viral gene transfer protocols.