Bjf. Hill et al., Effect of atorvastatin on intracellular calcium uptake in coronary smooth muscle cells from diabetic pigs fed an atherogenic diet, ATHEROSCLER, 159(1), 2001, pp. 117-124
Citations number
38
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
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 patient
s. Thus, we hypothesized that chronic atorvastatin treatment would prevent
increased Ca2+ uptake into intracellular Ca2+ stores in vascular smooth mus
cle cells from diabetic dyslipidemic pigs. Male Yucatan pigs were divided i
nto four groups for 20 weeks - (1) low fat fed (control); (2) hyperlipidemi
c (F), (3) alloxan-induced diabetic dyslipidemic (DF); and (4) diabetic dys
lipidemic pigs treated with atorvastatin (DFA). The F, DF, and DFA groups w
ere 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 th
e sarcoplasmic reticulum, SR) and ionomycin (10 muM; to release the total C
a2+ store) was determined in either the presence of low Na (19Na; inhibits
Na+-Ca2+ exchange), thapsigargin (TSG; inhibits the SR Ca2+ pump), and a 19
Na + TSG solution. Low Na induced the uptake of Ca2+ into both SR and non-S
R Ca2+ stores in the DF group, but not the DFA group. Furthermore, after de
pletion 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+ b
y SR and non-SR Ca2+ stores in diabetic dyslipidemic pigs. (C) 2001 Elsevie
r Science Ireland Ltd. All rights reserved.