Title
Altered <tex>$Ca^{2+}$</tex> handling of smooth muscle cells in aorta of apolipoprotein E-deficient mice before development of atherosclerotic lesions Altered <tex>$Ca^{2+}$</tex> handling of smooth muscle cells in aorta of apolipoprotein E-deficient mice before development of atherosclerotic lesions
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Edinburgh ,
Subject
Biology
Human medicine
Source (journal)
Cell calcium. - Edinburgh
Volume/pages
41(2007) :3 , p. 295-302
ISSN
0143-4160
ISI
000244770700010
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
To study the effect of hypercholesterolemia on vascular smooth muscle cell (VSMC) function, atherosclerosis-prone but plaque-free endothelium-denuded aortic rings (width 2 mm) from C57B16 Wild Type (WT) and apolipoprotein E-deficient (apoE(-/-)) mice (age 4 months) were mounted in a myograph and loaded with Fura-2 AM to simultaneously measure free Ca2+ ([Ca2+](i)) and force development. In comparison with WT, apoE(-/-) mice displayed higher basal [Ca2+](i). Moreover, the time constant of the second phase of the biphasic high K+-induced [Ca2+](i) response was significantly increased in apoE(-/-) compared to WT mice. This phase was abolished by treatment with cyclopiazonic acid (CPA), depleting sarcoplasmic reticulum (SR). Further investigation of SR dependent [Ca2+](i) handling with CPA and caffeine revealed no alteration of maximal SERCA or ryanodine receptor function. Inositol (1,4,5)-triphosphate receptor (IP3R)-mediated [Ca2+](i) release was, however, significantly increased in apoE(-/-) mice compared to WT mice as established with phenylephrine and ATP. In Ca2+-free conditions the ATP-induced [Ca2+](i) was not altered. The ATP-induced store-operated Ca2+ entry was, however, significantly increased in apoE(-/-) compared to WT mice. The results demonstrate that basal [Ca2+], levels and IP3R-mediated store-operated [Ca2+](i) release over the plasma membrane were elevated in hypercholesterolemic but plaque-free apoE(-/-) mice. (c) 2006 Elsevier Ltd. All rights reserved.
E-info
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