Effect of atorvastatin on intracellular calcium uptake in coronary smooth muscle cells from diabetic pigs fed an atherogenic diet
Effect of atorvastatin on intracellular calcium uptake in coronary smooth muscle cells from diabetic pigs fed an atherogenic diet
复制标题
DOI：
10.1016/s0021-9150(01)00501-9
复制
发表时间：
2001-11-01
期刊：
影响因子：
5.3
通讯作者：
Sturek, M
中科院分区：
文献类型：
--
作者：
Hill, BJF;Dixon, JL;Sturek, M
细胞内 Ca2+ 储存负荷已被证明可以改变几种细胞类型的增殖和凋亡。此外，HMG-CoA还原酶抑制剂（即阿托伐他汀）对于治疗糖尿病血脂异常患者也有效。因此，我们假设长期阿托伐他汀治疗可以防止糖尿病血脂异常猪的血管平滑肌细胞中 Ca2+ 细胞内 Ca2+ 储存的增加。将雄性尤卡坦猪分为四组，持续 20 周 - (1) 低脂喂养（对照）； (2)高脂血症(F)，(3)四氧嘧啶诱发的糖尿病血脂异常(DF)； (4)用阿托伐他汀(DFA)治疗的糖尿病血脂异常猪。 F、DF和DFA组喂食高脂肪/胆固醇饮食。从冠状动脉中分离细胞，并使用单细胞 fura-2 成像测量肌浆 Ca2+ (Ca-m) 反应。在低 Na（19Na；抑制 Na+-Ca2+ 交换）、毒胡萝卜素（TSG；抑制 SR Ca2+ 泵）和 19Na + TSG 溶液存在的情况下，测定对咖啡因（5 mM，从肌浆网释放 Ca2+，SR）和离子霉素（10 muM；释放总 Ca2+ 储存）的 Ca-m 反应。低 Na 诱导 DF 组中 SR 和非 SR Ca2+ 库吸收 Ca2+，但 DFA 组则不然。此外，在用 TSG 耗尽 SR Ca2+ 储存后，除 DFA 组外，所有三组中 19Na 都会引起 Ca2+ 摄取到非 SR Cal + 储存中。总之，本研究表明，阿托伐他汀可防止糖尿病血脂异常猪中 SR 和非 SR Ca2+ 储存对 Ca2+ 的增强吸收。 (C) 2001 Elsevier Science Ireland Ltd. 保留所有权利。
Intracellular Ca2+ store loading has been shown to alter proliferation and apoptosis of several cell types. In addition, HMG-CoA reductase inhibitors (i.e. atorvastatin) are effective in treating diabetic dyslipidemic patients. Thus, we hypothesized that chronic atorvastatin treatment would prevent increased Ca2+ uptake into intracellular Ca2+ stores in vascular smooth muscle cells from diabetic dyslipidemic pigs. Male Yucatan pigs were divided into four groups for 20 weeks - (1) low fat fed (control); (2) hyperlipidemic (F), (3) alloxan-induced diabetic dyslipidemic (DF); and (4) diabetic dyslipidemic pigs treated with atorvastatin (DFA). The F, DF, and DFA groups were fed a high fat/cholesterol diet. Cells were isolated from the coronary artery and the rnyoplasmic Ca2+ (Ca-m) response measured using single cell fura-2 imaging. The Ca-m response to caffeine (5 mM to release Ca2+ from the sarcoplasmic reticulum, SR) and ionomycin (10 muM; to release the total Ca2+ store) was determined in either the presence of low Na (19Na; inhibits Na+-Ca2+ exchange), thapsigargin (TSG; inhibits the SR Ca2+ pump), and a 19Na + TSG solution. Low Na induced the uptake of Ca2+ into both SR and non-SR Ca2+ stores in the DF group, but not the DFA group. Furthermore, after depletion of the SR Ca2+ store with TSG, 19Na evoked Ca2+ uptake into non-SR Cal + stores in all three groups except in the DFA group. In summary, this study demonstrates that atorvastatin prevents the enhanced uptake of Ca2+ by SR and non-SR Ca2+ stores in diabetic dyslipidemic pigs. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.