An overview of Apoe for application in gene therapy

Atherosclerosis, one of the most prevalent and severe age-related diseases, is the leading cause of death in industrialized countries and it is becoming an increasingly worldwide risk to health. As the size of elderly population grows, the incidence of atherosclerosis will increase, necessitating the exploration of radical, but potentially powerful, therapeutic strategies. One important goal is the availability of therapeutic molecules effective against the atherosclerotic plaque progression and able to stabilize advanced lesions. This generally requires robust measures to improve plasma lipoprotein profiles. Pharmaceutical agents currently available do not support significant changes in plasma lipoprotein levels. So that, strong new agents and therapies are needed in order to treat hyperlipidemia and atherosclerosis. Apolipoprotein E (ApoE), a key regulator in cholesterol-rich lipoprotein metabolism, is considered a strong candidate for treating hypercholesterolemia and cardiovascular disease. ApoE gene therapy could be proposed as a new valid approach for the correction of hyperlipidemic conditions and atherosclerosis by using viral and non-viral vectors. In this review we discuss the major developments in both viral and non-viral gene transfer systems aimed at achieving efficient protocols for treating hypercholesterolemia and atherosclerosis by using ApoE as therapeutic gene. Key scientific advances on the ability of ApoE gene transfer to markedly improve outcome after cerebral ischemia, suggesting a potential strategy in human stroke therapy, are also described in this review. The characterization of ApoE and its many functions has provided insight into the ultimate potential of this protein as a possible therapeutic agent for the treatment of several diseases. Possible therapeutic strategies that encompass the use of ApoE in gene therapy for Alzheimer's disease and other central nervous system (CNS) diseases will be also discussed.