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The BDNF rs6265 Polymorphism is a Modifier of Cardiomyocyte Contractility and Dilated Cardiomyopathy
- Source :
- International Journal of Molecular Sciences, Volume 21, Issue 20, International Journal of Molecular Sciences, Vol 21, Iss 7466, p 7466 (2020)
- Publication Year :
- 2020
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2020.
-
Abstract
- Brain-derived neurotrophic factor (BDNF) is a neuronal growth and survival factor that harbors cardioprotective qualities that may attenuate dilated cardiomyopathy. In ~30% of the population, BDNF has a common, nonsynonymous single nucleotide polymorphism rs6265 (Val66Met), which might be correlated with increased risk of cardiovascular events. We previously showed that BDNF correlates with better cardiac function in Duchenne muscular dystrophy (DMD) patients. However, the effect of the Val66Met polymorphism on cardiac function has not been determined. The goal of the current study was to determine the effects of rs6265 on BDNF biomarker suitability and DMD cardiac functions more generally. We assessed cardiovascular and skeletal muscle function in human DMD patients segregated by polymorphic allele. We also compared echocardiographic, electrophysiologic, and cardiomyocyte contractility in C57/BL-6 wild-type mice with rs6265 polymorphism and in mdx/mTR (mDMD) mouse model of DMD. In human DMD patients, plasma BDNF levels had a positive correlation with left ventricular function, opposite to that seen in rs6265 carriers. There was also a substantial decrease in skeletal muscle function in carriers compared to the Val homozygotes. Surprisingly, the opposite was true when cardiac function of DMD carriers and non-carriers were compared. On the other hand, Val66Met wild-type mice had only subtle functional differences at baseline but significantly decreased cardiomyocyte contractility. Our results indicate that the Val66Met polymorphism alters myocyte contractility, conferring worse skeletal muscle function but better cardiac function in DMD patients. Moreover, these results suggest a mechanism for the relative preservation of cardiac tissues compared to skeletal muscle in DMD patients and underscores the complexity of BDNF signaling in response to mechanical workload.
- Subjects :
- 0301 basic medicine
Duchenne muscular dystrophy
lcsh:Chemistry
Electrocardiography
Mice
0302 clinical medicine
Val66Met
Myocyte
Myocytes, Cardiac
lcsh:QH301-705.5
Spectroscopy
education.field_of_study
Dilated cardiomyopathy
General Medicine
rs6365 polymorphism
Computer Science Applications
medicine.anatomical_structure
Echocardiography
rs6265
Cardiac function curve
Cardiomyopathy, Dilated
musculoskeletal diseases
medicine.medical_specialty
brain-derived neurotrophic growth factor
Population
Mice, Transgenic
Polymorphism, Single Nucleotide
Catalysis
Article
Inorganic Chemistry
Contractility
03 medical and health sciences
Internal medicine
medicine
Animals
Humans
Genetic Predisposition to Disease
Physical and Theoretical Chemistry
education
Molecular Biology
Genetic Association Studies
business.industry
Brain-Derived Neurotrophic Factor
Organic Chemistry
Skeletal muscle
medicine.disease
Myocardial Contraction
dilated cardiomyopathy
Disease Models, Animal
030104 developmental biology
Endocrinology
Gene Expression Regulation
lcsh:Biology (General)
lcsh:QD1-999
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....7539cee170308687a9b493f7e915c5a5
- Full Text :
- https://doi.org/10.3390/ijms21207466