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Cardiomyocyte Contractile Dysfunction in the APPswe/ PS1dE9 Mouse Model of Alzheimer's Disease.
- Source :
- PLoS ONE; 2009, Vol. 4 Issue 6, p1-12, 12p, 1 Chart, 8 Graphs
- Publication Year :
- 2009
-
Abstract
- Objectives: Ample clinical and experimental evidence indicated that patients with Alzheimer's disease display a high incidence of cardiovascular events. This study was designed to examine myocardial histology, cardiomyocyte shortening, intracellular Ca<superscript>2+</superscript> homeostasis and regulatory proteins, electrocardiogram, adrenergic response, endoplasmic reticulum (ER) stress and protein carbonyl formation in C57 wild-type (WT) mice and an APPswe/PS1dE9 transgenic (APP/PS1) model for Alzheimer's disease. Methods: Cardiomyocyte mechanical properties were evaluated including peak shortening (PS), time-to-PS (TPS), time-torelengthening (TR), maximal velocity of shortening and relengthening (±dL/dt), intracellular Ca<superscript>2+</superscript> transient rise and decay. Results: Little histological changes were observed in APP/PS1 myocardium. Cardiomyocytes from APP/PS1 but not APP or PS1 single mutation mice exhibited depressed PS, reduced±dL/dt, normal TPS and TR compared with WT mice. Rise in intracellular Ca<superscript>2+</superscript> was lower accompanied by unchanged resting/peak intracellular Ca<superscript>2+</superscript> levels and intracellular Ca<superscript>2+</superscript> decay in APP/PS1 mice. Cardiomyocytes from APP/PS1 mice exhibited a steeper decline in PS at high frequencies. The responsiveness to adrenergic agonists was dampened although β<subscript>1</subscript>-adrenergic receptor expression was unchanged in APP/PS1 hearts. Expression of the Ca<superscript>2+</superscript> regulatory protein phospholamban and protein carbonyl formation were downregulated and elevated, respectively, associated with unchanged SERCA2a, Na+-Ca<superscript>2+</superscript> exchanger and ER stress markers in APP/PS1 hearts. Our further study revealed that antioxidant N-acetylcysteine attenuated the contractile dysfunction in APP/PS1 mice. Conclusions: Our results depicted overt cardiomyocyte mechanical dysfunction in the APP/PS1 Alzheimer's disease model, possibly due to oxidative stress. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 4
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 55982131
- Full Text :
- https://doi.org/10.1371/journal.pone.0006033