摘要:

Local gene transfer into the vascular wall offers a promising alternative to treat atherosclerosis‐related diseases at cellular and molecular levels. Blood vessels are among the easiest targets for gene therapy because of novel percutaneous, catheter‐based treatment methods. On the other hand, gene transfer to the artery wall can also be accomplished from adventitia, and in some situations intramuscular gene delivery is also a possibility. In most conditions, such as postangioplasty restenosis, only a temporary expression of the transfected gene will be required. Promising therapeutic effects have been obtained in animal models of restenosis with the transfer of genes for vascular endothelial growth factor, fibroblast growth factor, thymidine kinase, p53, bcl‐x, nitric oxide synthase and retinoblastoma. Also, growth arrest homeobox gene and antisense oligonucleotides against transcription factors or cell cycle regulatory proteins have produced beneficial therapeutic effects. Angiogenesis is an emerging new target for gene therapy of ischemic diseases. In addition, hyperlipoproteinemias may be improved by transferring functional lipoprotein‐receptor genes into hepatocytes of affected individuals. First experiences of gene transfer methods in the human vascular system have been reported. However, further studies regarding gene delivery methods, vectors and safety of the procedures are needed before a full therapeutic potential of gene therapy in vascular diseases can be evaluated. Curr Opin Lipidol 9:465–469. © 1998 Lippincott Williams & Wilkins

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Many lines of evidence indicate that the key initiating event in early atherosclerosis is the subendothelial retention of cholesterol‐rich, atherogenic lipoproteins. Once retained, these lipoproteins provoke a cascade of responses that lead to disease in a previously non‐lesional artery. We review recent experimental work that has substantially reinforced this hypothesis. Lipoprotein retention has been shown to be a pivotal requirement in the murine model of atherosclerosis: low‐density lipoprotein, engineered through site‐directed mutagenesis of apolipoprotein‐B100to bind poorly to arterial proteoglycans, causes relatively few lesionsin vivo, even during significant hyperlipidemia. In addition, many molecules in the arterial wall that are involved in the retention of atherogenic lipoproteins and in arterial responses to retained material have recently been characterized. Overall, the response‐to‐retention hypothesis can now be regarded as a central paradigm in our understanding of the pathogenesis of this deadly disease. Curr Opin Lipidol 9:471–474. © 1998 Lippincott Williams & Wilkins

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0957-9672    

出版商:OVID    

年代:1998

数据来源: OVID