β1-Adrenoceptor antibodies induce PPCM via inhibition of PGC-1α related pathway

Abstract

Objectives: Peripartum cardiomyopathy (PPCM) is a pregnancy-associated and life-threatening cardiac disease. However, the causes and pathogenesis are not fully understood. Accumulating studies show that cardiomyopathy often appears to be associated with elevated levels of β1-adrenoceptor (β1AR) antibodies, indicating a possible involvement of β1AR antibodies in the development of PPCM. Design: We injected the antigen peptide segment of the β1AR into the postpartum Wistar rats to make the immune models and their cardiac function was detected by echocardiography. Also, the concentration of β1AR antibodies and apoptosis rate of left ventricular myocytes was tested by SA-ELISA, TUNEL, HE staining, qRT-PCR and western blot methods. Finally, the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and its related proteins were examined by qRT-PCR and western blot methods. Results: We found that the level of β1AR antibodies in the serum was significantly increased and the postpartum rats exhibited symptoms of PPCM after autoimmunity. Moreover, the expression of peroxisome PGC-1α, which was a master regulator of mitochondrial metabolism, and its downstream transcript vascular endothelial growth factor (VEGF), was decreased in autoimmune perinatal rats. In addition, the expression of the apoptosis factor caspase 3 as well as the apoptosis rate of left ventricular myocytes was significantly increased. Conclusions: The results suggested that the symptoms of PPCM that appeared in autoimmune perinatal rats may be due to the increase of β1AR antibodies, which inhibited the pathway associated with peroxisome PGC-1α.