title: Long-term administration of rosuvastatin prevents contractile and electrical remodelling of diabetic rat heart.
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. I(CaL) 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 I(to) and I(sus) was also reversed, whilst I(K1) 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.
authors: Department of Biophysics, Akdeniz University Faculty of Medicine, Antalya, Turkey.
authors: Nihal
authors: N
authors: Ozturk
authors: Nazmi
authors: N
authors: Yaras
authors: Asli
authors: A
authors: Ozmen
authors: Semir
authors: S
authors: Ozdemir
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005464:Fluorobenzenes / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000068718:Rosuvastatin Calcium; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D020742:rhoA GTP-Binding Protein; D002118:Calcium
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