ß1 adrenoceptor antibodies induce myocardial apoptosis via inhibiting PGC-1α-related pathway.
BMC Cardiovasc Disord
; 20(1): 269, 2020 06 05.
Article
in En
| MEDLINE
| ID: mdl-32503464
ABSTRACT
BACKGROUND:
Peripartum cardiomyopathy (PPCM) is life-threatening heart disease. However, the causes and pathogenesis of PPCM remain unclear. Previous studies found that ß1 adrenoceptor antibodies (ß1AA) had possible involvement in the development of PPCM. In the present study, we determined the potential relationship between PPCM and ß1AA, including the mechanism of ß1AA leading to PPCM.METHODS:
We extracted the ß1AA from the postpartum Wistar rats that were injected by the antigen peptide segment of the ß1 adrenoceptor to produce PPCM. We tested the effects of ß1AA on H9C2 cell line by CCK-8, LDH, TUNEL, SA-ELISA, qRT-PCR, and western blot methods. Furthermore, PGC-1α was overexpressed to rescue the effect of ß1AA on H9C2 cells.RESULTS:
We found that the extracted ß1AA induced apoptosis of cardiac myocytes of H9C2 cell line. Moreover, the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which is a master regulator of mitochondrial metabolism, and its downstream transcript vascular endothelial growth factor (VEGF) got decreased in H9C2 cells after ß1AA treatment. In addition, the effect of ß1AA could be inhibited by atenolol, the antagonist of ß1 adrenoceptors (ß1AR) and imitated by isoprenaline, the agonist of ß1AR. Furthermore, overexpression of PGC-1α in the H9C2 cells rescued the apoptosis of cells and inhibitory expression of VEGF induced by ß1AA.CONCLUSIONS:
Our results suggest that the symptoms of PPCM due to myocardial cell apoptosis induced by ß1AA inhibiting the PGC-1α-related pathway impairs mitochondrial energy metabolism. Therefore, our results uncover a previously unknown role of the ß1AA pathway in the etiology of PPCM and provide a novel potential target for the treatment of PPCM.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pregnancy Complications, Cardiovascular
/
Apoptosis
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Receptors, Adrenergic, beta-1
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Myocytes, Cardiac
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
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Antibodies
/
Cardiomyopathies
Limits:
Animals
/
Pregnancy
Language:
En
Journal:
BMC Cardiovasc Disord
Journal subject:
ANGIOLOGIA
/
CARDIOLOGIA
Year:
2020
Document type:
Article
Affiliation country:
China