Molecular and cellular changes during development of cardiac fibrosis in cardiomyopathy

心肌病是一组异质性疾病，其特征在于泵衰竭和恶性心律失常;它们通常与遗传异常相关。死亡率很高，在诊断后的前5年内高达45-60%。治疗选择包括多模式医疗、双心室起搏器、机械辅助装置和心脏移植。大量的纤维化病理发展是所有心肌病的重要组织学（和病理生理学）特征。纤维化是由细胞外基质（主要是胶原蛋白）的产生增加和降解减少引起的，最终导致心脏不良重塑。这些心肌结构变化与收缩和/或舒张功能障碍和心律失常有关。最近的研究证明，成纤维细胞和心脏巨噬细胞是主要的病理驱动因素，因为它们共同的转录变化;然而，这些变化在不同类型的心肌病之间是不同的。因此，波士顿的研究工作将重点关注成纤维细胞和心脏巨噬细胞的起源/迁移，它们的分子激活/抑制途径，以及最后但并非最不重要的可能的治疗靶点。

Cardiomyopathies are a heterogeneous group of diseases, characterised by pump failure and malignant arrhythmias; they are frequently associated with genetic abnormalities. Mortality is high and up to 45-60% within the first 5 years after diagnosis. Therapeutic options include multimodal medical treatments, biventricular pacemakers, mechanical assist devices and heart transplantations. Abundant pathologic development of fibrosis is a crucial histologic (and pathophysiological) feature of all cardiomyopathies. Fibrosis is caused by an increased production and decreased degradation of the extracellular matrix (mostly collagen), which finally causes cardiac adverse remodeling. These myocardial structural changes are associated with systolic and/or diastolic dysfunctions and arrhythmias. Recent investigations proved that fibroblasts and cardiac macrophages are the major pathologic drivers due to their common transcriptional changes; these changes, however, differ in between different types of cardiomyopathies. The research work in Boston will therefore focus on the origins/migrations of fibroblasts and cardiac macrophages, their molecular activation/suppression pathways and last but not least on possible therapeutic targets.