Bone vasculature provides protection and signals necessary to control stem cell quiescence and renewal (1). Specifically, type H capillaries, which highly express Endomucin, constitute the endothelial niche supporting a microenvironment of osteoprogenitors and long term hematopoietic stem cells (2 - 4). The age dependent decline in type H endothelial cells was shown to be associated with bone dysregulation and accumulation of hematopoietic stem cells, which display cellintrinsic alterations and reduced functionality (3). The regulation of bone vasculature by chronic diseases, such as heart failure is unknown. Here, we describe the effects of myocardial infarction and post infarction heart failure on the vascular bone cell composition. We demonstrate an age independent loss of type H bone endothelium in heart failure after myocardial infarction in both mice and in humans. Using singlecell RNA sequencing, we delineate the transcriptional heterogeneity of human bone marrow endothelium showing increased expression of inflammatory genes, including IL1B and MYC, in ischemic heart failure. Inhibition of NLRP3 dependent IL-1β production partially prevents the post myocardial infarction loss of type H vasculature in mice. These results provide a rationale for using anti-inflammatory therapies to prevent or reverse the deterioration of vascular bone function in ischemic heart disease.

中文翻译：

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心肌梗塞后心力衰竭对骨小生境的影响

骨脉管系统提供了控制干细胞静止和更新所需的保护和信号（1）。具体而言，高表达Endomucin的H型毛细血管构成了支持骨祖细胞和长期造血干细胞微环境的内皮位（2-4）。H型内皮细胞的年龄依赖性衰老与骨失调和造血干细胞蓄积有关，造血干细胞表现出细胞内在的改变和功能的降低（3）。慢性疾病如心力衰竭对骨脉管系统的调节是未知的。在这里，我们描述了心肌梗塞和梗塞后心力衰竭对血管骨细胞组成的影响。我们在小鼠和人类的心肌梗死后的心力衰竭中证明了H型骨内皮细胞的年龄独立损失。使用单细胞RNA测序，我们描绘了人类骨髓内皮细胞的转录异质性，显示在缺血性心力衰竭中炎症基因（包括IL1B和MYC）的表达增加。抑制NLRP3依赖性IL-1β的产生可部分预防小鼠H型脉管系统心肌梗死后的丢失。这些结果为使用抗炎疗法预防或逆转缺血性心脏病中血管骨骼功能的恶化提供了理论依据。包括缺血性心力衰竭的IL1B和MYC。抑制NLRP3依赖性IL-1β的产生可部分预防小鼠H型脉管系统心肌梗死后的丢失。这些结果为使用抗炎疗法预防或逆转缺血性心脏病中血管骨骼功能的恶化提供了理论依据。包括缺血性心力衰竭的IL1B和MYC。抑制NLRP3依赖性IL-1β的产生可部分预防小鼠H型脉管系统心肌梗死后的丢失。这些结果为使用抗炎疗法预防或逆转缺血性心脏病中血管骨骼功能的恶化提供了理论依据。