研究人员对一组不同的近交系小鼠的转录组和功能数据进行的系统遗传学分析表明，凝血因子XI（FXI），一种来自肝脏的蛋白，可以防止舒张功能障碍，这是保留射血分数的心衰的一个关键特征。这一点通过功能增益和功能缺失研究得到证实，并发现FXI能激活心脏中的骨形态发生蛋白（BMP）-SMAD1/5途径。FXI的蛋白水解活性对于心脏中细胞外基质相关BMP7的切割和激活是所需的，从而抑制了参与炎症和纤维化的基因。这些结果揭示了FXI在心脏损伤中的保护作用，这与它在凝血中的作用不同。
据悉，内分泌因子的组织-组织交流是生理平衡的一个重要机制。
附：英文原文
Title: Liver-heart cross-talk mediated by coagulation factor XI protects against heart failure
Author: Yang Cao, Yuchen Wang, Zhenqi Zhou, Calvin Pan, Ling Jiang, Zhiqiang Zhou, Yonghong Meng, Sarada Charugundla, Tao Li, Hooman Allayee, Marcus M. Seldin, Aldons J. Lusis
Issue&Volume: 2022-09-23
Abstract: 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.
DOI: abn0910
Source: https://www.science.org/doi/10.1126/science.abn0910