Rosuvastatin Alleviates Type 2 Diabetic Atrial Structural and Calcium Channel Remodeling.
Recent evidence has indicated that type 2 diabetes mellitus is related to an increased risk of atrial arrhythmias, which might result from atrial structural and electrical remodeling. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (statins), known as lipid-lowering agents, have been shown to exert antiarrhythmic effects both in experimental models and in humans. In this study, we postulate that atrial structural and calcium channel remodeling may occur in streptozotocin-induced type 2 diabetic rats and can be alleviated by rosuvastatin (RSV) therapy. We randomly divided Wistar rats into control, untreated diabetic, RSV-treated control, and RSV-treated diabetic animals. After treatment with RSV for 4 weeks, rats were assessed by metabolic tests, histopathology, and transmission electron microscopy. The expression of Cav1.2, Cav3.1, and Cav3.2 in atrial tissues was detected by real-time reverse transcriptase polymerase chain reaction and Western blot, and inward calcium currents (l(Ca-L) and l(Ca-T)) were recorded in isolated atrial myocytes using patch-clamp techniques. Compared with controls, diabetic rats displayed severe metabolic disorders and a disorganized cellular ultrastructure. In diabetic rats, the expression of Cav1.2 mRNA and protein was significantly decreased, whereas that of Cav3.1 was significantly increased. Long-term RSV treatment partially relieved some pathological changes in diabetic rats. However, Cav3.2 mRNA and protein remained unchanged in control and diabetic groups and was unaffected by RSV. Diabetic atrial myocytes showed significantly reduced L-type but increased T-type, Ca (2+) currents, and this effect was significantly reversed by RSV. In conclusion, long-term RSV therapy can alleviate structural and calcium channel remodeling in the type 2 diabetic rat atrium.
Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, China.
Yilong
Y
Pan
Bin
B
Li
Jingzhuo
J
Wang
Xiaodong
X
Li
D000818:Animals; D020746:Calcium Channels, L-Type / Q000096:biosynthesis*; D020747:Calcium Channels, T-Type / Q000096:biosynthesis*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D000068718:Rosuvastatin Calcium / Q000494:pharmacology / Q000627:therapeutic use*
C500994:Cacna1g protein, rat; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C419385:L-type calcium channel alpha(1C); D000068718:Rosuvastatin Calcium