Mechanosensitive genes regulate multiple cardiovascular pathophysiological processes and disorders; however, the role of flow-sensitive genes in atherosclerosis is still unknown. In this study, we identify LIM Zinc Finger Domain Containing 2 (LIMS2) that acts as a mechanosensitive gene downregulated by disturbed flow (d-flow) both in human endothelial cells (ECs) in vitro and in mice in vivo. Mechanistically, d-flow suppresses LIMS2 expression, which leads to endothelial inflammation by upregulating typical inflammatory factors, VCAM-1, and ICAM-1 in human ECs. The findings indicate that LIMS2, the new flow-sensitive gene, may help us to find a new insight to explain how d-flow caused endothelial inflammation and provide a new therapeutic approach for atherosclerosis in the future.

Impact statement

Whereas we all know that atherosclerosis is the most main common reason of death all over the world, the mechanism of atherosclerosis is still unclear. Recently, more and more evidence indicate that atherosclerosis is a kind of flow-dependent disease, and plenty of mechanosensitive genes have been mentioned in it. Here, we identified for the first time that LIMS2 is a novel flow-sensitive gene and inhibits inflammation by modulating inflammatory factors, VCAM-1, and ICAM-1 in endothelial cells. It will help us to understand the connection between endothelial shear stress and endothelial inflammation deeply; certainly, LIMS2 may also act as a potential target for flow-dependent atherosclerosis.

中文翻译：

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流体剪切应力通过靶向 LIMS2 调节内皮炎症。

机械敏感基因调节多种心血管病理生理过程和障碍；然而，血流敏感基因在动脉粥样硬化中的作用仍然未知。在这项研究中，我们确定了含有 2 的 LIM 锌指结构域 (LIMS2)，该基因在体外人内皮细胞 (EC)和小鼠体内均作为受扰流 (d-flow) 下调的机械敏感基因。从机制上讲，d-flow 抑制 LIMS2 表达，从而通过上调人内皮细胞中典型的炎症因子、VCAM-1 和 ICAM-1 导致内皮炎症。研究结果表明，新的血流敏感基因LIMS2可能有助于我们找到新的见解来解释d-flow如何引起内皮炎症，并为未来的动脉粥样硬化提供新的治疗方法。

影响陈述

虽然我们都知道动脉粥样硬化是全世界最常见的死亡原因，但动脉粥样硬化的机制仍不清楚。近年来，越来越多的证据表明动脉粥样硬化是一种血流依赖性疾病，其中提到了大量的机械敏感基因。在这里，我们首次发现 LIMS2 是一种新型的血流敏感基因，它通过调节内皮细胞中的炎症因子、VCAM-1 和 ICAM-1 来抑制炎症。有助于我们深入了解内皮剪切应力与内皮炎症之间的联系；当然，LIMS2 也可能作为血流依赖性动脉粥样硬化的潜在靶点。