PDF(Pubmed)
Abstract：
In patients with Fabry disease (FD), cardiovascular involvement is the main cause of death and reduction of quality of life. Left ventricular hypertrophy mimicking hypertrophic cardiomyopathy is the main feature of FD cardiac involvement although glycolipid storage occurs in all cardiac cellular types. Accumulation of lysosomal globotriasylceramide represents the main mechanism of cardiac damage in early stages, but secondary pathways of cellular and tissue damage, triggered by lysosomal storage, and including altered energy production, inflammation and cell death, contribute to cardiac damage and disease progression. These mechanisms appear prominent in more advanced stages, hampering and reducing the efficacy of FD-specific treatments. Therefore, additional cardiovascular therapies are important to manage cardiovascular symptoms and reduce cardiovascular events. Although new therapies targeting lysosomal storage are in development, a better definition and comprehension of the complex pathophysiology of cardiac damage in FD, may lead to identify new therapeutic targets beyond storage and new therapeutic strategies.
摘要：
在Fabry病（FD）患者中，心血管受累是导致死亡和生活质量下降的主要原因。模拟肥厚型心肌病的左心室肥大是FD心脏受累的主要特征，尽管糖脂储存发生在所有心脏细胞类型中。溶酶体球形神经酰胺的积累代表了早期心脏损伤的主要机制，但是细胞和组织损伤的次级途径，由溶酶体储存引发，包括改变的能源生产，炎症和细胞死亡，有助于心脏损伤和疾病进展。这些机制在更高级的阶段显得突出，妨碍和降低FD特异性治疗的疗效。因此,额外的心血管治疗对于控制心血管症状和减少心血管事件非常重要.尽管针对溶酶体贮积的新疗法正在开发中，更好地定义和理解FD中心脏损害的复杂病理生理学，可能导致确定新的治疗靶点超越储存和新的治疗策略。
