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.

中文翻译：

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β1-肾上腺素能受体抗体通过抑制 PGC-1α 相关通路诱导 PPCM

摘要

目标

围产期心肌病 (PPCM) 是一种妊娠相关且危及生命的心脏病。然而，病因和发病机制尚不完全清楚。越来越多的研究表明，心肌病似乎通常与 β1-肾上腺素能受体 (β1AR) 抗体水平升高有关，表明 β1AR 抗体可能参与 PPCM 的发展。

设计

我们将β1AR的抗原肽段注射到产后Wistar大鼠中制作免疫模型，并通过超声心动图检测其心功能。同时，通过SA-ELISA、TUNEL、HE染色、qRT-PCR和蛋白质印迹方法检测β1AR抗体浓度和左心室肌细胞凋亡率。最后，通过qRT-PCR和蛋白质印迹方法检测过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）及其相关蛋白的表达。

结果

我们发现血清中β1AR抗体水平显着升高，产后大鼠在自身免疫后表现出PPCM症状。此外，作为线粒体代谢主要调节因子的过氧化物酶体 PGC-1α 及其下游转录物血管内皮生长因子 (VEGF) 在自身免疫围生期大鼠中的表达降低。此外，凋亡因子caspase 3的表达以及左心室肌细胞的凋亡率显着增加。

结论

结果提示，自身免疫性围生期大鼠出现PPCM的症状可能是由于β1AR抗体增加，抑制了与过氧化物酶体PGC-1α相关的通路。