Gene transfer into cardiovaseluar system using AAV vectors

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We tried to use adeno-associated virus (AAV) vectors for gene therapy of various cardiovascular diseases such as pulmonary hypertension and cardiac hypertrophy. With a Grant-in-Aid for Scientific Research c, we revealed following new findings.(I) Transfer of AA V vectors into cardiovascular cells We first prepared AAV-LacZ . This AAV-LacZ could be transduced into rat vascular smooth muscles and cardiac myocytes with high efficiency. Furthermore, the expression of transduced LacZ gene persisted more than 2 weeks.(ii) ecNOS gene transfer into 293 cells We transduced endothelial nitric oxide synthase (ecNOS) gene into human embryonic kidney cell line 293 cells. The ecNOS protein expression was observed in the transfected cells, and ecNOS gene transfer markedly inhibited endothelin-1-induced proliferation of 293 cells.(iii) ecNOS gene transfer into cardiac myocytes We transduced AAV-ecNOS into rat cardiac myocytes. The ecNOS gene transfer significantly inhibited phenylephrine-induced protein synthesis of cardiac myocytes, which was recovered in the presence of the NOS inhibitor L-NMMA.Above findings suggest that ecNOS gene transfer using AAV vectors is useful for treatment of pulmonary hypertension and cardiac hypertrophy.