Terapia Genética para Hipertensão (Inglês)

M. Ian Phillips, Department of Physiology, College of Medicine, Box 100274, University of Florida, Gainesville, FL 32610, Phone: 352-392-7730, Fax: 352-392-8340, E-Mail: MIP@phys.med.ufl.edu. . Two approaches to gene therapy for hypertension in cardiovascular disease are being tested in our laboratory. One is oligonucleotides, and the second is viral vectors to deliver antisense DNA. Antisense oligodeoxynucleotides (AS.ODN) are effective in reducing blood pressure in rat models of hypertension. Compared to currently used anti-hypertensive drugs, the effects of AS.ODN are longer-lasting. They can be given systemically and control hypertension without adverse effect. Repeated injections can be given and there is sustained decrease in hypertension. Specifically, the AS.ODNs have been designed to inhibit AT1 receptors, angiotensinogen, angiotensin converting enzyme, and beta-1 adrenergic receptor. Antisense to AT1R and beta-1 receptor also provide beneficial effects in heart tissue after ischemia-reperfusion injury. . . Adeno-associated virus (AAV) vectors deliver antisense DNA for very prolonged periods with a single systemic injection. In adult, transgenic, hypertensive mice blood pressure was significantly reduced for more than 6 months with a single dose. The vector was expressed throughout this period. In summary, AS.ODNs, which are cheap to manufacture, ...

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