Tissue-tissue communication by endocrine factors is a vital mechanism for physiologic homeostasis. A systems genetics analysis of transcriptomic and functional data from a cohort of diverse, inbred strains of mice predicted that coagulation factor XI (FXI), a liver-derived protein, protects against diastolic dysfunction, a key trait of heart failure with preserved ejection fraction. This was confirmed using gain- and loss-of-function studies, and FXI was found to activate the bone morphogenetic protein (BMP)–SMAD1/5 pathway in the heart. The proteolytic activity of FXI is required for the cleavage and activation of extracellular matrix–associated BMP7 in the heart, thus inhibiting genes involved in inflammation and fibrosis. Our results reveal a protective role of FXI in heart injury that is distinct from its role in coagulation.

中文翻译：

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凝血因子 XI 介导的肝心串扰可预防心力衰竭

内分泌因子的组织间通讯是生理稳态的重要机制。对一组不同近交系小鼠的转录组和功能数据进行的系统遗传学分析预测，凝血因子 XI (FXI)（一种肝源性蛋白质）可以预防舒张功能障碍，这是射血分数保留的心力衰竭的一个关键特征。通过功能获得和功能丧失研究证实了这一点，并且发现 FXI 可以激活心脏中的骨形态发生蛋白 (BMP)-SMAD1/5 通路。FXI 的蛋白水解活性是心脏中细胞外基质相关 BMP7 的裂解和激活所必需的，从而抑制与炎症和纤维化有关的基因。我们的结果揭示了 FXI 在心脏损伤中的保护作用，与其在凝血中的作用不同。