Mitochondrial Dynamics in Tachycardiomyopathy.
Biopsy
Cardiomyopathy, Dilated
/ classification
Dynamins
GTP Phosphohydrolases
/ genetics
Gene Expression Regulation
Heart Rate
/ physiology
Humans
Membrane Proteins
/ genetics
Microtubule-Associated Proteins
/ genetics
Mitochondria
/ genetics
Mitochondrial Dynamics
/ genetics
Mitochondrial Membrane Transport Proteins
/ genetics
Mitochondrial Proteins
/ genetics
Mitophagy
/ genetics
Myocytes, Cardiac
/ metabolism
Peptide Elongation Factors
/ genetics
Protein Kinases
/ genetics
RNA, Messenger
/ genetics
Fusion
Heart failure
Mfn1
Mfn2
Mitochondria
TCM
Tachycardiomyopathy
Journal
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
ISSN: 1421-9778
Titre abrégé: Cell Physiol Biochem
Pays: Germany
ID NLM: 9113221
Informations de publication
Date de publication:
2019
2019
Historique:
received:
13
08
2018
accepted:
07
01
2019
entrez:
16
3
2019
pubmed:
16
3
2019
medline:
20
3
2019
Statut:
ppublish
Résumé
Tachycardiomyopathy (TCM) is a largely reversible form of non-ischemic heart failure. The underlying mechanism are, however, still today poorly understood. Recent data indicate distinct changes in mitochondrial distribution in these patients, compared to other non-ischemic cardiomyopathies.This study investigated underlying mechanisms in mitochondrial dynamics in endomyocardial biopsy samples (EMB) from patients with TCM and compared them to patients with dilated cardiomyopathy (DCM), which show similar clinical features. Focused mRNA analyses were performed on routinely obtained paraffinfixed EMB specimen from patients fulfilling TCM diagnosis criteria, as well as patients with DCM to elucidate regulatory changes in mitochondrial fusion, fission and mitophagy. In patients with TCM we were able to identify mRNA of Mitofusin 1 and 2, two effector proteins regulating mitochondrial fusion, to be strongly upregulated compared to patients with DCM. Conclusively, we did not find differences in the mRNA expression of mitochondrial fission regulators including DRP1, Fis1, MFF, MiD49, and MiD51. Furthermore, we did not find significant changes in PINK1 expression, an important mediator for mitochondrial autophagy. The mRNA upregulation of Mitofusin 1 and 2 provides first insight into the complex changes of mitochondrial dynamics in cardiomyocytes of patients with reversible heart failure due to TCM.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
Tachycardiomyopathy (TCM) is a largely reversible form of non-ischemic heart failure. The underlying mechanism are, however, still today poorly understood. Recent data indicate distinct changes in mitochondrial distribution in these patients, compared to other non-ischemic cardiomyopathies.This study investigated underlying mechanisms in mitochondrial dynamics in endomyocardial biopsy samples (EMB) from patients with TCM and compared them to patients with dilated cardiomyopathy (DCM), which show similar clinical features.
METHODS
METHODS
Focused mRNA analyses were performed on routinely obtained paraffinfixed EMB specimen from patients fulfilling TCM diagnosis criteria, as well as patients with DCM to elucidate regulatory changes in mitochondrial fusion, fission and mitophagy.
RESULTS
RESULTS
In patients with TCM we were able to identify mRNA of Mitofusin 1 and 2, two effector proteins regulating mitochondrial fusion, to be strongly upregulated compared to patients with DCM. Conclusively, we did not find differences in the mRNA expression of mitochondrial fission regulators including DRP1, Fis1, MFF, MiD49, and MiD51. Furthermore, we did not find significant changes in PINK1 expression, an important mediator for mitochondrial autophagy.
CONCLUSION
CONCLUSIONS
The mRNA upregulation of Mitofusin 1 and 2 provides first insight into the complex changes of mitochondrial dynamics in cardiomyocytes of patients with reversible heart failure due to TCM.
Substances chimiques
FIS1 protein, human
0
MIEF1 protein, human
0
MIEF2 protein, human
0
Membrane Proteins
0
Mff protein, human
0
Microtubule-Associated Proteins
0
Mitochondrial Membrane Transport Proteins
0
Mitochondrial Proteins
0
Peptide Elongation Factors
0
RNA, Messenger
0
Protein Kinases
EC 2.7.-
PTEN-induced putative kinase
EC 2.7.11.1
GTP Phosphohydrolases
EC 3.6.1.-
MFN2 protein, human
EC 3.6.1.-
Mfn1 protein, human
EC 3.6.5.-
DNM1L protein, human
EC 3.6.5.5
Dynamins
EC 3.6.5.5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
435-438Subventions
Organisme : German Research Foundation
ID : 374031971
Pays : Germany
Organisme : German Research Foundation
ID : Klinische Forschungsgruppe 274: Platelets - Molecular Mechanisms and Translational Implications
Pays : Germany
Organisme : German Research Foundation
ID : Collaborative Research Center Transregio 240
Pays : Germany
Informations de copyright
© Copyright by the Author(s). Published by Cell Physiol Biochem Press.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.