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Beta-1 adrenergic receptor antisense-oligodeoxynucleotides ameliorates left ventricular remodeling in 2-Kidney, 1-Clip rats

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Journal of Biomedical Science

Abstract

Gene therapy has been applied to reduce blood pressure in rats. However, little is known about the effects of gene therapy on both blood pressure and left ventricular (LV) remodeling. This study was designed to compare the antihypertensive effect of ß1 adrenergic receptor antisense oligodeoxynucleotides (ß1- AS-ODN) by delivery with the different charge ratios cationic liposomes DOTAP/DOPE and its impact on the LV remodeling in rats with 2-Kidney, 1-Clip (2K1C) Hypertension. Five charge ratios of liposome/ODN were tested in 2K1C rats. There was hypertension, cardiac dysfunction, LV hypertrophy and LV collagen deposition in 2K1C rats. On the basis of the magnitude and duration of hypotension, 2.0 was determined to be the optimal charge ratio, which decreased blood pressure by up to 39 mm Hg for 27 days. ß1-AS-ODN preserved cardiac function and inhibited LV mass and LV interstitial collagen deposition. In conclusion, cationic liposomes DOTAP/DOPE improve the antihypertensive effects of ß1-AS-ODN in renovascular hypertension and 2.0 were determined to be the optimal charge ratio. This study demonstrated that cardiac ß1-AR played a key role in LV remodeling and ß1-AS-ODN ameliorates cardiac dysfunction and LV remodeling.

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Correspondence to Shuguang Lin or Yan Zhou.

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Liang, Y., Lin, S., Zhou, Y. et al. Beta-1 adrenergic receptor antisense-oligodeoxynucleotides ameliorates left ventricular remodeling in 2-Kidney, 1-Clip rats. J Biomed Sci 14, 155–164 (2007). https://doi.org/10.1007/s11373-006-9128-0

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  • DOI: https://doi.org/10.1007/s11373-006-9128-0

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