The functional role of TGFβ type I receptor, activin-like kinase (ALK)-1 in post-myocardial infarction (MI) cardiac remodeling is unknown. We hypothesize that reduced ALK1 activity reduces survival and promotes cardiac fibrosis after MI. MI was induced in wild-type (WT), and ALK^+/− mice by left coronary ligation. After 14 days ALK1^+/− mice had reduced survival with a higher rate of cardiac rupture compared to WT mice. ALK1^+/− left ventricles (LVs) had increased volumes at the end of systole and at the end of diastole. After MI ALK1^+/− LVs had increased profibrotic SMAD3 signaling, type 1 collagen, and fibrosis as well as increased levels of TGFβ1 co-receptor, endoglin, VEGF, and ALK1 ligands BMP9 and BMP10. ALK1^+/− LVs had decreased levels of stromal-derived factor 1α. These data identify the critical role of ALK1 in post-MI survival and cardiac remodeling and implicate ALK1 as a potential therapeutic target to improve survival after MI.

Graphical abstract

中文翻译：

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ALK1 缺乏会损害心肌梗塞小鼠模型的伤口愈合过程并增加死亡率

TGFβ I 型受体、激活素样激酶 (ALK)-1 在心肌梗死 (MI) 后心脏重塑中的功能作用尚不清楚。我们假设 ALK1 活性降低会降低 MI 后的存活率并促进心脏纤维化。通过左冠状动脉结扎在野生型 (WT) 和 ALK ^+/-小鼠中诱导 MI 。14 天后，与 WT 小鼠相比，ALK1 ^+/-小鼠的存活率降低，心脏破裂率更高。ALK1 ^+/-左心室 (LV) 在收缩期末和舒张期末容积增加。MI 后，ALK1 ^+/- LV 促纤维化 SMAD3 信号传导、1 型胶原和纤维化增加，TGFβ1 共受体、内皮糖蛋白、VEGF 和 ALK1 配体 BMP9 和 BMP10 水平增加。ALK1 ^+/- LV 的基质衍生因子 1α 水平降低。这些数据确定了 ALK1 在 MI 后生存和心脏重塑中的关键作用，并表明 ALK1 作为改善 MI 后生存的潜在治疗靶点。

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