Characterization of the role of inflammation in the pathogenesis and prognosis of patients with peripartum cardiomyopathy (PPCM)

围产期心肌病（PPCM）是扩张型心肌病的一种形式，其中先前健康的女性在怀孕的最后几个月或分娩后长达5个月期间因左心室（LV）功能障碍而出现心力衰竭。在世界范围内，这种疾病影响大约1/1000的怀孕，但其患病率在不同地区和种族之间存在显着差异。临床表现从中度心力衰竭症状到严重心源性休克，需要重症监护治疗。PPCM的病因和发病机制仍不清楚，需要进一步研究。通过很大程度上未知的机制，氧化应激水平的增加导致妊娠激素催乳素裂解成16 kDa的片段，其（通过复杂的信号传导途径）导致内皮功能障碍并最终导致心肌细胞死亡。这些炎症、抗血管生成和促凋亡过程似乎发生在具有潜在遗传易感性的患者中，尽管大多数女性在12个月后恢复了心脏功能，但其他人仍然持续降低LV功能，导致慢性心力衰竭。由于仍然难以预测哪些患者将恢复左心室功能，未来的研究应旨在更好地描述影响PPCM患者结局的因素。这对于患有这种疾病的女性的风险分层和最佳管理至关重要。在我的研究项目中，我想研究炎症在PPCM发病机制中的作用，并评估其对预后的影响。作为我研究的一部分，我计划对PPCM患者的血液样本进行蛋白质分析（蛋白质组学）。通过这样做，我想探索新的炎症（生物）标记物，可能在PPCM的发展中发挥作用。 此外，通过磁共振成像（MRI）和正电子发射断层扫描/计算机断层扫描（PET-CT），我想研究这种情况下的炎症程度（即PPCM中的炎症是否仅限于心脏或是否与全身炎症有关）。我还计划研究PPCM中炎症程度和对药物敏感性增加之间是否存在关联。最后，我打算进行遗传分析，看看炎症相关基因是否在PPCM女性中上调，以及这是否可以解释他们对这种疾病的可能遗传易感性。

Peripartum cardiomyopathy (PPCM) is a form of dilated cardiomyopathy, in which previously healthy women present with heart failure due to left ventricular (LV) dysfunction during the last months of pregnancy or up to 5 months after delivery. Worldwide, the disease affects approximately 1 in 1000 pregnancies, however its prevalence differs significantly between different regions and ethnicities. Clinical presentation ranges from moderate heart failure symptoms to severe cardiogenic shock, which requires intensive care treatment.The aetiology and pathogenesis of PPCM remain poorly understood and require further research. Through largely unknown mechanisms, increased levels of oxidative stress cause a cleavage of the pregnancy hormone prolactin into a 16kDa fragment, which (through complex signaling pathways) causes endothelial dysfunction and ultimately results in cardiomyocyte death. These inflammatory, anti-angiogenic and pro-apoptotic processes seem to occur in patients with an underlying genetic susceptibility.Even though the majority of the women recover their cardiac function after 12 months, others remain with a persistently reduced LV function leading to chronic heart failure. As it remains difficult to predict which patients would recover their LV function, future research should aim at better characterisation of the factors that influence the outcome of patients with PPCM. This is crucial for the risk-stratification and optimal management of women with this condition.In my research project, I would like to to study the role of inflammation in the pathogenesis of PPCM and to characterise its impact on prognosis.As part of my research, I plan to perform a protein analysis (proteomics) on blood samples collected from patients with PPCM. By doing so, I would like to explore new inflammatory (bio-)markers that might play a role in the development of PPCM. Furthermore, by means of magnetic resonance imaging (MRI) and positron emission tomography / computed tomography (PET-CT), I would like to study the extent of inflammation in this condition (i.e. whether inflammation in PPCM is limited to the heart or whether the condition is associated with systemic inflammatory involvement). I also plan to study whether there is an association between the degree of inflammation and the increased susceptibility to arrhythmic events in PPCM. Finally, I intend to perform a genetic analysis, to see whether inflammation-related genes are up-regulated in women with PPCM and whether this could explain their possible genetic susceptibility of this condition.