Cardiac Immune cell TargEting of LYMPHatics

心脏炎症是心血管疾病(CVD)的共同特征，也是心力衰竭(HF)发生的重要原因。我们最近证明了心脏淋巴管作为一种新的治疗靶点来减少心脏炎症的潜力。在这个项目中，我们将描述免疫细胞和心脏淋巴管之间的相互联系，重点放在炎症淋巴管中的分子变化，这些变化可能导致缺血型和非缺血型心血管疾病免疫反应的低分辨率，特别是趋化因子表达的变化。此外，我们将研究内源性淋巴管生成抑制因子的作用。最后，我们将确定通过优化的淋巴管生成治疗预防淋巴管稀疏和功能障碍是否可以恢复受损的心脏心血管疾病的淋巴功能，限制心脏炎症和改善心脏恢复。我们预计，对心脏修复协调中免疫细胞-淋巴干扰的研究将揭示更好地预防和治疗心脏炎症和心力衰竭的新的分子靶点。

Cardiac inflammation, a common trait in cardiovascular diseases (CVDs), contributes to the development of heart failure (HF). We recently demonstrated the potential of cardiac lymphatics as a novel therapeutic target to reduce cardiac inflammation. In this project, we will characterize the interconnection between immune cells and cardiac lymphatics, focusing on molecular changes in inflamed lymphatics that may cause poor resolution of the immune response in ischemic vs non-ischemic CVDs, notably alterations in chemokine expression. Further, we will investigate the role of endogenous lymphangiogenesis inhibitors. Finally, we will determine whether prevention of lymphatic rarefaction and dysfunction, by optimized lymphangiogenic therapy, may restore lymphatic function, limit cardiac inflammation and improve cardiac recovery of the injured heart CVDs. We anticipate that investigations of the immune cell-lymphatic cross-talk in orchestration of cardiac repair will reveal new molecular targets for better prevention and treatment of cardiac inflammation and HF.