Research Progress Of Viral Vectors For Gene Therapy Of Atherosclerosis

Gene therapy for atherosclerosis is still in the preclinical stage, except for a pilot study of the LDL receptor gene to prevent early atherosclerosis in patients with familial hypercholesterolemia conducted about 20 years ago. Potential gene therapy for atherosclerosis involves manipulation of plasma lipoproteins to prevent or reverse the growth of atherosclerotic lesions through gene transfer to the liver and direct gene transfer to the vessel wall. This article will introduce the mechanism of action of one of viral vectors for gene therapy of atherosclerosis-Adenovirus vector.

Adenovirus-mediated vein transplantation for the treatment of atherosclerosis

Cardiovascular disease has been the leading cause of death and disability for many years, especially heart disease caused by atherosclerosis. The morbidity and mortality of atherosclerosis is the most common cause of coronary artery involvement, where accumulation of intimal lipids and inflammatory cells leads to lumen narrowing, reduced blood flow, and thrombotic occlusion, accompanied by chest pain, myocardial infarction, Associated symptoms such as heart failure and sudden death. At present, the drugs used to prevent graft atherosclerosis are mainly lipid-lowering drugs, represented by statins. Statins are used in the vast majority of coronary artery bypass graft recipients; however, there is no evidence that widespread statin use increases vein graft patency rates, and there is evidence that patency rates are declining. Furthermore, statin therapy is only partially effective: statin-induced lowering of LDL cholesterol to so the viral vectors for gene therapy of atherosclerosis by vascular transplantation are promising vectors for the further development.

Adenoviral vector-mediated transfection of prothymosin-α gene inhibits atherosclerosis

Oxidative stress, caused by the reduction of antioxidants or the overproduction of reactive oxygen species, is considered to be the primary mechanism in the pathogenesis of endothelial dysfunction and the initiation and progression of atherosclerosis. Defense mechanisms that scavenge intravascular reactive oxygen species and inhibit nitric oxide degradation include enzymatic catalase, superoxide dismutase, and glutathione peroxidase, as well as non-enzymatic low molecular weight groups. Nitric oxide is the major vasodilator and is synthesized by endothelial nitric oxide synthase. Superoxide promotes cellular damage by reacting with vascular nitric oxide or reducing vascular nitric oxide bioavailability. Since the vascular level of superoxide is regulated by superoxide dismutase, the role of superoxide dismutase gene in cardiovascular disease is of great significance.

Prothymosin alpha is a small, highly acidic protein that is distributed in the nuclei of various tissues and is highly conserved in mammals. Numerous studies have demonstrated the immunomodulatory functions of prothymosin alpha, including enhancing the expression of human major histocompatibility antigen class II surface antigens on antigen-presenting cells and the cytotoxicity of human natural killer cells. In addition, prothymosin alpha may have broader effects on transcription, affecting the activity of specific transcription factors, including estrogen receptor and signal transducer and activator of transcription 3. In some studies, the effect of prothymosin alpha gene transfection on the expression of antioxidant genes was examined using adenovirus expressing prothymosin alpha to investigate the protective effect of prothymosin alpha mediated endothelial cell oxidative damage in vitro and in vivo.

Summary

In recent years, viral vectors for gene therapy of atherosclerosis have indeed made significant progress. But there are still some potential problems with this research. With the further in-depth study of viral molecular biology and the comprehensive understanding of the pathogenesis of atherosclerosis, viral vectors that meet the needs will be introduced into the clinic in the future, providing new ideas for the treatment of cardiovascular system diseases. In conclusion, the kind of viral vectors for gene therapy will become a powerful tool due to its unique advantages that other viral vectors cannot match.