Spontaneously Hypertensive Rat (SHR) provides a useful experimental model of pressure overload that gradually develops hypertension. This model has demonstrated many similarities with human essential hypertension, including the development of cardiac hypertrophy (CH) [1]. In a previous work we demonstrated that long chain n-3 polyunsaturated fatty acids (LC-PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), modulate the expression of genes related to CH in cultured cardiomyocytes [2]. Recently it has been demonstrated that n-3 LC-PUFAs attenuate cardiac pathology in response to pressure overload [3] appear particularly interesting. In this study we evaluated the effects of a n-3 LC-PUFA supplemented diet on cardiac global gene expression profile in SH and control (Wistar-Kyoto, WK) rats. Fourteen WK and 14 SH rats were randomly divided into two groups. One group was fed a standard diet and the other one was fed the same diet supplemented with n-3 LC-PUFAS. Blood pressure was recorded at 0, 30, 60, and 90 days. After 90 days, rats were weighted, anesthetized and killed. Blood samples were obtained, and hearts were excised, weighted and the left ventricles separated and stored at -80°C. RNA was extracted from left ventricles and analysed using the Affymetrix Expression Analysis Protocol. Validation of selected genes was performed by quantitative one step Real-Time PCR. EPA and DHA dietary supplementation normalized blood pressure in SH rats. Heart weight, significantly higher in SH rats consuming the control diet, decreased towards normal value in hypertensive rats fed LC-PUFAs. In the left ventricle, about 280 genes appeared modulated by EPA and DHA supplementation. Some of these appeared to have a role in the protection or induction of CH, cardiac remodelling or heart failure (HF). Overall, our analysis showed that WK and SH rats have a substantive different gene expression profile, and in SH animals n-3 LC-PUFA supplementation induces a shift towards WK profile. This study represents the first report on the modulation of global gene expression in SH rats; the encouraging results provide a great hope that n-3 LC-PUFAs might contribute to novel adjunctive therapeutic approaches for human CH and HF. This work was supported by a grant of SPA Antibiotics SpA. References: [1] E.D. Frohlich and M.A. Pfeffer (1975) Clin Sci Mol Med Suppl 2: 225s-238s. [2] Bordoni A. et al (2007) FEBS Lett 581: 923-929. [3] O'Shea KM et al (2010) Lipids Health Dis 6;9:95.
de Biase, D., Danesi, F., Astolfi, A., Goldoni, A., Morandi, L., Pession, A., et al. (2011). n-3 LC-PUFAs modulate global gene expression in the left ventricle of spontaneously hypertensive rats. Bologna : Alma Mater Studiorum - Università di Bologna.
n-3 LC-PUFAs modulate global gene expression in the left ventricle of spontaneously hypertensive rats
DE BIASE, DARIO;DANESI, FRANCESCA;ASTOLFI, ANNALISA;GOLDONI, ALBERTO;MORANDI, LUCA;PESSION, ANDREA;PESSION, ANNALISA;BORDONI, ALESSANDRA
2011
Abstract
Spontaneously Hypertensive Rat (SHR) provides a useful experimental model of pressure overload that gradually develops hypertension. This model has demonstrated many similarities with human essential hypertension, including the development of cardiac hypertrophy (CH) [1]. In a previous work we demonstrated that long chain n-3 polyunsaturated fatty acids (LC-PUFAs), namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), modulate the expression of genes related to CH in cultured cardiomyocytes [2]. Recently it has been demonstrated that n-3 LC-PUFAs attenuate cardiac pathology in response to pressure overload [3] appear particularly interesting. In this study we evaluated the effects of a n-3 LC-PUFA supplemented diet on cardiac global gene expression profile in SH and control (Wistar-Kyoto, WK) rats. Fourteen WK and 14 SH rats were randomly divided into two groups. One group was fed a standard diet and the other one was fed the same diet supplemented with n-3 LC-PUFAS. Blood pressure was recorded at 0, 30, 60, and 90 days. After 90 days, rats were weighted, anesthetized and killed. Blood samples were obtained, and hearts were excised, weighted and the left ventricles separated and stored at -80°C. RNA was extracted from left ventricles and analysed using the Affymetrix Expression Analysis Protocol. Validation of selected genes was performed by quantitative one step Real-Time PCR. EPA and DHA dietary supplementation normalized blood pressure in SH rats. Heart weight, significantly higher in SH rats consuming the control diet, decreased towards normal value in hypertensive rats fed LC-PUFAs. In the left ventricle, about 280 genes appeared modulated by EPA and DHA supplementation. Some of these appeared to have a role in the protection or induction of CH, cardiac remodelling or heart failure (HF). Overall, our analysis showed that WK and SH rats have a substantive different gene expression profile, and in SH animals n-3 LC-PUFA supplementation induces a shift towards WK profile. This study represents the first report on the modulation of global gene expression in SH rats; the encouraging results provide a great hope that n-3 LC-PUFAs might contribute to novel adjunctive therapeutic approaches for human CH and HF. This work was supported by a grant of SPA Antibiotics SpA. References: [1] E.D. Frohlich and M.A. Pfeffer (1975) Clin Sci Mol Med Suppl 2: 225s-238s. [2] Bordoni A. et al (2007) FEBS Lett 581: 923-929. [3] O'Shea KM et al (2010) Lipids Health Dis 6;9:95.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
