PDF(Pubmed)
Abstract：
Altered ankyrin-R (AnkR; encoded by ANK1) expression is associated with diastolic function, left ventricular remodeling, and heart failure with preserved ejection fraction (HFpEF). First identified in erythrocytes, the role of AnkR in other tissues, particularly the heart, is less studied. Here, we identified the expression of both canonical and small isoforms of AnkR in the mouse myocardium. We demonstrate that cardiac myocytes primarily express small AnkR (sAnkR), whereas cardiac fibroblasts predominantly express canonical AnkR. As canonical AnkR expression in cardiac fibroblasts is unstudied, we focused on expression and localization in these cells. AnkR is expressed in both the perinuclear and cytoplasmic regions of fibroblasts with considerable overlap with the trans-Golgi network protein 38, TGN38, suggesting a potential role in trafficking. To study the role of AnkR in fibroblasts, we generated mice lacking AnkR in activated fibroblasts (Ank1-ifKO mice). Notably, Ank1-ifKO mice fibroblasts displayed reduced collagen compaction, supportive of a novel role of AnkR in normal fibroblast function. At the whole animal level, in response to a heart failure model, Ank1-ifKO mice displayed an increase in fibrosis and T-wave inversion compared with littermate controls, while preserving cardiac ejection fraction. Collagen type I fibers were decreased in the Ank1-ifKO mice, suggesting a novel function of AnkR in the maturation of collagen fibers. In summary, our findings illustrate the novel expression of AnkR in cardiac fibroblasts and a potential role in cardiac function in response to stress.
摘要：
Ankyrin-R(AnkR;由ANK1编码)表达改变与舒张功能相关,左心室重构,射血分数保留的心力衰竭（HFpEF）。首先在红细胞中发现，AnkR在其他组织中的作用，尤其是心脏，研究较少。这里,我们确定了小鼠心肌中AnkR的经典和小亚型的表达。我们证明心肌细胞主要表达小AnkR（sAnkR），而心脏成纤维细胞主要表达经典AnkR。由于心脏成纤维细胞中的经典AnkR表达尚未研究，我们专注于在这些细胞中的表达和定位。AnkR在成纤维细胞的核周和细胞质区域均表达，与反式高尔基体网络蛋白38TGN38相当重叠，表明在运输中具有潜在作用。研究AnkR在成纤维细胞中的作用,我们在激活的成纤维细胞中产生了缺乏AnkR的小鼠（Ank1-ifKO小鼠）。值得注意的是,Ank1-ifKO小鼠成纤维细胞显示胶原蛋白压缩减少，支持AnkR在正常成纤维细胞功能中的新作用。在整个动物层面，作为对心力衰竭模型的回应，与同窝对照相比，Ank1-ifKO小鼠显示纤维化和T波倒置增加，同时保留心脏射血分数。Ank1-ifKO小鼠的I型胶原纤维减少，提示AnkR在胶原纤维成熟中的新功能。总之,我们的发现说明了AnkR在心脏成纤维细胞中的新表达以及在应激反应的心脏功能中的潜在作用。
