Reese-Petersen Alexander L, Genovese Federica, Zhao Lei, Banks Glen, Gordon David A, Karsdal Morten A
Nordic Bioscience A/S, Herlev, Denmark.
Bristol Myers Squibb, New York, NJ, United States.
Front Mol Biosci. 2023 Jul 12;10:1228232. doi: 10.3389/fmolb.2023.1228232. eCollection 2023.
Extracellular matrix proteins harbor signaling domains that once released from the parent molecule can trigger cellular responses. One of these molecules is endotrophin, a type VI collagen derived fragment, whose circulatory levels have been associated to an increased risk of adverse outcome in heart failure with preserved ejection fraction (HFpEF). Here we show that the stimulation of human cardiac fibroblasts by endotrophin upregulates the synthesis of type I collagen, the main interstitial collagen that accumulates in the myocardium during fibrogenesis. These data provide a possible mechanistic explanation for the relation between circulating endotrophin levels and risk of outcome in HFpEF.
细胞外基质蛋白含有信号结构域，一旦从母体分子中释放出来，就可以触发细胞反应。其中一种分子是内养蛋白，一种VI型胶原衍生片段，其循环水平与射血分数保留的心力衰竭（HFpEF）不良结局风险增加有关。在这里，我们表明内养蛋白对人心脏成纤维细胞的刺激上调了I型胶原的合成，I型胶原是纤维生成过程中在心肌中积累的主要间质胶原。这些数据为循环内养蛋白水平与HFpEF结局风险之间的关系提供了一种可能的机制解释。
