Conclusions and Therapeutic Perspectives
Each cell type in the myocardium interacts with another in various ways and has its own unique changes to gene and
protein expression, protein secretion and response to signals from other cells (Figure 1). It has become clear that the myofibroblast is a significantly more complex cell type that was initially appreciated. Moreover, the ECM has emerged as a dynamic component in both the normal and diseased heart. Despite recent progress, our understanding of many of these cell–cell and cell–ECM interactions remains unclear.
Cytokine antagonists, particularly those targeting TNF , did not provide any apparent clinical benefit in HF patients, despite the promising preclinical data, but targeting the role of inflammatory cytokine signalling in HF has provided fruitful lessons for future drug development. Moreover, it would be highly beneficial to identify pharmacologic agents that might inhibit myofibroblast formation in chronic disease states while sparing their protective role in physiological wound healing. One particularly important aspect of cell–cell cross-talk in the heart is the CM–EC interactions. Once our understanding of how changes in endothelial cell mass affect cardiac hypertrophy improves, we may gain more insight into the possibility of stimulating angiogenesis and vessel growth in the injured myocardium.
Further research into the dynamic intercellular communication is crucial for the development of novel therapeutic strategies that target directly HF disease progression.