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Title
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Altered handling of smooth muscle cells in aorta of apolipoprotein E-deficient mice before development of atherosclerotic lesions
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Cell calcium. - Edinburgh
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Publication
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Edinburgh
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2007
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ISSN
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0143-4160
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DOI
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10.1016/J.CECA.2006.06.010
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Volume/pages
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41
:3
(2007)
, p. 295-302
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ISI
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000244770700010
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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