Abstract
BackgroundPeripartum cardiomyopathy (PPCM) is life-threatening heart disease. However, the causes and pathogenesis of PPCM remain unclear. Previous studies found that β1 adrenoceptor antibodies (β1AA) had possible involvement in the development of PPCM. In the present study, we determined the potential relationship between PPCM and β1AA, including the mechanism of β1AA leading to PPCM.MethodsWe extracted the β1AA from the postpartum Wistar rats that were injected by the antigen peptide segment of the β1 adrenoceptor to produce PPCM. We tested the effects of β1AA 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 β1AA on H9C2 cells.ResultsWe found that the extracted β1AA 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 β1AA treatment. In addition, the effect of β1AA could be inhibited by atenolol, the antagonist of β1 adrenoceptors (β1AR) and imitated by isoprenaline, the agonist of β1AR. Furthermore, overexpression of PGC-1α in the H9C2 cells rescued the apoptosis of cells and inhibitory expression of VEGF induced by β1AA.ConclusionsOur results suggest that the symptoms of PPCM due to myocardial cell apoptosis induced by β1AA inhibiting the PGC-1α-related pathway impairs mitochondrial energy metabolism. Therefore, our results uncover a previously unknown role of the β1AA pathway in the etiology of PPCM and provide a novel potential target for the treatment of PPCM.
Highlights
Peripartum cardiomyopathy (PPCM) is life-threatening heart disease
We examined the effects of extractive β1 adrenoceptor antibodies (β1AA) on survival and apoptosis in myocardial H9C2 cells and the expression of β1 adrenoceptors (β1AR), caspase3, PGC-1α, and vascular endothelial growth factor (VEGF), which is the downstream transcript of PGC-1α
Validation of extractive β1AA To investigate the effect of β1AA on the PPCM first, β1AA were extracted from the autoimmune postpartum Wistar rats by using the Affinity chromatography method
Summary
We extracted the β1AA from the postpartum Wistar rats that were injected by the antigen peptide segment of the β1 adrenoceptor to produce PPCM. Β1AA were extracted from the postpartum Wistar rats, which were injected the antigen peptide segment of the β1 adrenoceptor to produce autoimmunity and the effects of extracted β1AA on the H9C2 cells were examined. Animals and active immunity Ten postpartum Wistar rats were obtained from Model Animal Research Center of Nanjing University, maintained in specific pathogen-free (SPF) conditions under a 12 h-light-12 h-dark cycle. The antigenic peptide segment of β1 adrenoceptor was purchased from GL Biochem company (Shanghai, China). The mixture was injected subcutaneously in back of each animal with antigenic peptide segment 0.4 μg/g. Intravenous blood samples were performed on each groups in the third week. The animals were euthanized with intraperitoneal injection of excessive pentobarbital (100-150 mg/kg)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
