Gene-based therapy for hypertension--do preclinical data suggest a promising future?
Many experimental studies have obtained a prolonged control of blood pressure through gene treatment. This consists in the administration of genes coding for vasodilator proteins (the 'sense' approach), or of nucleotide sequences that are complementary to the mRNA of vasoconstrictor proteins, which are consequently synthesized in smaller amounts (the 'antisense' approach). Examples of the sense approach include the genes encoding endothelial nitric oxide synthase and kallikrein. Examples of the second type of approach are the antisense oligodeoxynucleotides to angiotensin-converting enzyme and endothelin-1. Also, RNA molecules, such as ribozymes and small interfering RNAs, are capable to inhibit RNA function. Whole sense genes are usually administered through viral vectors, while antisense oligonucleotides may be administered with plasmids or liposomes. Both viral and non-viral vectors have advantages and disadvantages. Despite the still persisting limitations, the possibility exists that in the future some forms of genetic treatment will be extended to the clinical setting, allowing a prolonged control of essential hypertension and its end-organ sequelae.
Puddu
Giovanni Maria
GM
Department of Internal Medicine and Aging, S. Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Cravero
Eleonora
E
Ferrari
Eleonora
E
Muscari
Antonio
A
Puddu
Paolo
P
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005544:Forecasting; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000628:therapy*; D008297:Male; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000235:genetics; D012307:Risk Factors; D012680:Sensitivity and Specificity
D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering