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Cardiomyocyte contractile dysfunction in the APPswe/PS1dE9 mouse model of Alzheimer's disease
- Source :
- PLoS ONE, Vol 4, Iss 6, p e6033 (2009), PLoS ONE
- Publication Year :
- 2009
- Publisher :
- Public Library of Science (PLoS), 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(2+) 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-to-relengthening (TR), maximal velocity of shortening and relengthening (+/-dL/dt), intracellular Ca(2+) 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(2+) was lower accompanied by unchanged resting/peak intracellular Ca(2+) levels and intracellular Ca(2+) 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 beta(1)-adrenergic receptor expression was unchanged in APP/PS1 hearts. Expression of the Ca(2+) regulatory protein phospholamban and protein carbonyl formation were downregulated and elevated, respectively, associated with unchanged SERCA2a, Na(+)-Ca(2+) 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.
- Subjects :
- Male
Amyloid
medicine.medical_specialty
Receptor expression
Cardiovascular Disorders/Heart Failure
Adrenergic
lcsh:Medicine
Mice, Transgenic
Biology
Endoplasmic Reticulum
medicine.disease_cause
Electrocardiography
Mice
03 medical and health sciences
0302 clinical medicine
Muscular Diseases
Alzheimer Disease
Internal medicine
mental disorders
medicine
Animals
Humans
Myocyte
Maze Learning
lcsh:Science
030304 developmental biology
0303 health sciences
Multidisciplinary
Endoplasmic reticulum
Physiology/Cardiovascular Physiology and Circulation
lcsh:R
Phospholamban
Mice, Inbred C57BL
Disease Models, Animal
Endocrinology
Unfolded protein response
Calcium
lcsh:Q
Neurological Disorders/Alzheimer Disease
030217 neurology & neurosurgery
Homeostasis
Oxidative stress
Research Article
Muscle Contraction
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 4
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....8f2d3e9a0e50e7fae11a68ab5c06f5fd