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Synergism of simvastatin with losartan prevents angiotensin II-induced cardiomyocyte apoptosis in vitro.
J Pharm Pharmacol. 2009 Apr; 61(4):503-10.JP

Abstract

OBJECTIVES

Increasing evidence suggests that cardiomyocyte apoptosis has an important role in the transition from compensatory cardiac remodelling to heart failure. The synergistic effect of statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) and angiotensin II (Ang II) type 1 receptor antagonists reduces the incidence of cardiovascular events. However, the anti-apoptotic potential of the synergism between losartan and simvastatin in heart failure remains unexplored. Here, we demonstrate that Ang II-induced apoptosis is prevented by losartan and simvastatin in neonatal cardiomyocytes.

METHODS

The in-vitro cardiomyocyte apoptosis model was established by co-culturing neonate rat cardiomyocytes with Ang II. Cell viability was analysed by the MTT assay. Cell apoptosis was evaluated using fluorescence microscopy and flow cytometry. Apoptosis-related proteins Bax and Bcl-2 expressions were measured by flow cytometry detection.

KEY FINDINGS

Incubation with 10(-7) M Ang II for 48 h increased cardiomyocyte apoptosis and decreased cell viability. Losartan (10(-5) M) and simvastatin (10(-5) M), either alone or in combination, significantly decreased Ang II-induced cardiomyocyte apoptosis and increased cell viability. The q values calculated by the probability sum test were 1.31 for cardiomyocyte apoptosis and 1.21 for cell viability. Ang II induced a significant increase in Bax protein expression, whereas Bcl-2 protein expression was decreased. Losartan alone or in combination with simvastatin blocked the increased Bax expression and increased Bcl-2 expression. However, simvastatin had no such effect.

CONCLUSIONS

Our data provide the first evidence that synergism of simvastatin with losartan prevents angiotensin II-induced cardiomyocyte apoptosis in vitro. Synergism between simvastatin and losartan may provide a new therapeutic approach to the prevention of cardiac remodelling.

Authors+Show Affiliations

School of Pharmacy, Anhui Medical University, Hefei, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19298698

Citation

Xu, Jian, et al. "Synergism of Simvastatin With Losartan Prevents Angiotensin II-induced Cardiomyocyte Apoptosis in Vitro." The Journal of Pharmacy and Pharmacology, vol. 61, no. 4, 2009, pp. 503-10.
Xu J, Lü XW, Huang Y, et al. Synergism of simvastatin with losartan prevents angiotensin II-induced cardiomyocyte apoptosis in vitro. J Pharm Pharmacol. 2009;61(4):503-10.
Xu, J., Lü, X. W., Huang, Y., Zhu, P. L., & Li, J. (2009). Synergism of simvastatin with losartan prevents angiotensin II-induced cardiomyocyte apoptosis in vitro. The Journal of Pharmacy and Pharmacology, 61(4), 503-10. https://doi.org/10.1211/jpp/61.04.0013
Xu J, et al. Synergism of Simvastatin With Losartan Prevents Angiotensin II-induced Cardiomyocyte Apoptosis in Vitro. J Pharm Pharmacol. 2009;61(4):503-10. PubMed PMID: 19298698.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synergism of simvastatin with losartan prevents angiotensin II-induced cardiomyocyte apoptosis in vitro. AU - Xu,Jian, AU - Lü,Xiong-Wen, AU - Huang,Yan, AU - Zhu,Peng-Li, AU - Li,Jun, PY - 2009/3/21/entrez PY - 2009/3/21/pubmed PY - 2009/6/9/medline SP - 503 EP - 10 JF - The Journal of pharmacy and pharmacology JO - J Pharm Pharmacol VL - 61 IS - 4 N2 - OBJECTIVES: Increasing evidence suggests that cardiomyocyte apoptosis has an important role in the transition from compensatory cardiac remodelling to heart failure. The synergistic effect of statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) and angiotensin II (Ang II) type 1 receptor antagonists reduces the incidence of cardiovascular events. However, the anti-apoptotic potential of the synergism between losartan and simvastatin in heart failure remains unexplored. Here, we demonstrate that Ang II-induced apoptosis is prevented by losartan and simvastatin in neonatal cardiomyocytes. METHODS: The in-vitro cardiomyocyte apoptosis model was established by co-culturing neonate rat cardiomyocytes with Ang II. Cell viability was analysed by the MTT assay. Cell apoptosis was evaluated using fluorescence microscopy and flow cytometry. Apoptosis-related proteins Bax and Bcl-2 expressions were measured by flow cytometry detection. KEY FINDINGS: Incubation with 10(-7) M Ang II for 48 h increased cardiomyocyte apoptosis and decreased cell viability. Losartan (10(-5) M) and simvastatin (10(-5) M), either alone or in combination, significantly decreased Ang II-induced cardiomyocyte apoptosis and increased cell viability. The q values calculated by the probability sum test were 1.31 for cardiomyocyte apoptosis and 1.21 for cell viability. Ang II induced a significant increase in Bax protein expression, whereas Bcl-2 protein expression was decreased. Losartan alone or in combination with simvastatin blocked the increased Bax expression and increased Bcl-2 expression. However, simvastatin had no such effect. CONCLUSIONS: Our data provide the first evidence that synergism of simvastatin with losartan prevents angiotensin II-induced cardiomyocyte apoptosis in vitro. Synergism between simvastatin and losartan may provide a new therapeutic approach to the prevention of cardiac remodelling. SN - 0022-3573 UR - https://www.unboundmedicine.com/medline/citation/19298698/Synergism_of_simvastatin_with_losartan_prevents_angiotensin_II_induced_cardiomyocyte_apoptosis_in_vitro_ L2 - https://doi.org/10.1211/jpp/61.04.0013 DB - PRIME DP - Unbound Medicine ER -