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Protein Aggregates and Novel Presenilin Gene Variants in Idiopathic Dilated Cardiomyopathy
- Source :
- Circulation. 121:1216-1226
- Publication Year :
- 2010
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2010.
-
Abstract
- Background— Heart failure is a debilitating condition resulting in severe disability and death. In a subset of cases, clustered as idiopathic dilated cardiomyopathy (iDCM), the origin of heart failure is unknown. In the brain of patients with dementia, proteinaceous aggregates and abnormal oligomeric assemblies of β-amyloid impair cell function and lead to cell death. Methods and Results— We have similarly characterized fibrillar and oligomeric assemblies in the hearts of iDCM patients, pointing to abnormal protein aggregation as a determinant of iDCM. We also showed that oligomers alter myocyte Ca 2+ homeostasis. Additionally, we have identified 2 new sequence variants in the presenilin-1 ( PSEN1 ) gene promoter leading to reduced gene and protein expression. We also show that presenilin-1 coimmunoprecipitates with SERCA2a. Conclusions— On the basis of these findings, we propose that 2 mechanisms may link protein aggregation and cardiac function: oligomer-induced changes on Ca 2+ handling and a direct effect of PSEN1 sequence variants on excitation-contraction coupling protein function.
- Subjects :
- Adult
Cardiomyopathy, Dilated
Male
Amyloid
medicine.medical_specialty
Cardiomyopathy
Protein aggregation
Biology
medicine.disease_cause
Polymorphism, Single Nucleotide
Article
Presenilin
Physiology (medical)
Internal medicine
Presenilin-2
Idiopathic dilated cardiomyopathy
Presenilin-1
medicine
PSEN1
Humans
Aged
Mutation
Amyloid beta-Peptides
Proteins
Dilated cardiomyopathy
Middle Aged
medicine.disease
Immunohistochemistry
Cell biology
Endocrinology
Heart failure
Calcium
Female
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 15244539 and 00097322
- Volume :
- 121
- Database :
- OpenAIRE
- Journal :
- Circulation
- Accession number :
- edsair.doi.dedup.....45c90a1d2b91ffe4b1b1da65bc5017d7