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Long-term administration of rosuvastatin prevents contractile and electrical remodelling of diabetic rat heart

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Abstract

In recent years, many findings have been presented about the potential benefit of statin therapy on diabetes-induced cardiovascular complications. Cardioprotective effects of statins were suggested to be mediated at least in part through inhibition of small GTPases, particularly those of the Rho family. The present study was designed to examine whether rosuvastatin can improve electrical remodeling and contractile dysfunction in type 1 diabetic rat heart via modulation of RhoA pathway. Type 1 diabetes was induced by single dose injection of STZ (50 mg/kg). One week after injection rosuvastatin (10 mg/kg/day) and sham treatment was given for 5 weeks in the diabetic rats, as well as in control groups. Shortening and Ca2+ transients were recorded in myocytes loaded with Fura2-AM. Membrane currents and Ca2+ transients were measured synchronously via whole-cell patch clamping. In untreated diabetic rats, relaxation of shortening and decay of the matched Ca2+ transients were prolonged. Fractional shortening and Ca2+ transients were also decreased. Rosuvastatin treatment reversed those changes. ICaL density did not change in either group but rosuvastatin recovered the loss of sarcoplasmic reticulum Ca2+ and Na+/Ca2+ exchange as evidenced from amplitude and decay of caffeine-induced Ca2+ transients, peak INCX and calculated sarcoplasmic reticulum Ca2+ content. Diabetes-induced attenuation of Ito and Isus was also reversed, whilst IK1 was unchanged in diabetes and unaffected by treatment. Rosuvastatin prevented the diabetes-induced increase in RhoA expression. Plasma cholesterol and triglyceride levels were higher in diabetic rats, but rosuvastatin reduced only the latter. In conclusion, HMG-CoA reductase inhibitor rosuvastatin can prevent diabetes-induced electrical and functional remodeling of heart due to inhibition of RhoA signalling rather than reduction of cholesterol level.

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Authors and Affiliations

  1. Department of Biophysics, Akdeniz University Faculty of Medicine, Antalya, Turkey

    Nihal Ozturk, Nazmi Yaras & Semir Ozdemir

  2. Department of Histology and Embryology, Akdeniz University Faculty of Medicine, Antalya, Turkey

    Asli Ozmen

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  1. Nihal Ozturk
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  2. Nazmi Yaras
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  3. Asli Ozmen
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  4. Semir Ozdemir
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Correspondence to Semir Ozdemir.

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Ozturk, N., Yaras, N., Ozmen, A. et al. Long-term administration of rosuvastatin prevents contractile and electrical remodelling of diabetic rat heart. J Bioenerg Biomembr 45, 343–352 (2013). https://doi.org/10.1007/s10863-013-9514-z

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  • DOI: https://doi.org/10.1007/s10863-013-9514-z

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