Cardiovasc Diabetol:糖化ACE2可降低糖尿病患者心脏中RAS系统抑制的抗重构作用

2022-08-08 MedSci原创 MedSci原创

实现严格的血糖控制可使 RAS 抑制的抗重构作用正常化

在射血分数降低的 2 型糖尿病 (T2DM) 患者中,虽然肾素-血管紧张素系统 (RAS) 受到抑制,但高糖化血红蛋白 (HbA1c) 水平与不良心血管结局的风险升高相关。通过对 T2DM 受者进行非 T2DM 心脏移植 (HTX) 的常规活检,该研究评估了糖尿病环境是否会调节已知受非酶糖基化影响的心肌细胞中的糖基化 ACE2 (GlycACE2) 水平,以及其与血糖控制的关系。

研究人员通过评估人心脏中的血管紧张素(Ang)1-9、Ang1-7和Mas受体(MasR)活化 T 细胞核因子 (NFAT) 和纤维化水平来研究GlycACE2对Ras抑制剂的抗重构通路的潜在影响。

共纳入了197位首次 HTX 受者(107位非T2DM患者和90位T2DM患者)。所有患者都接受血管紧张素转换酶抑制剂(ACE-I)或血管进展素受体阻滞剂(ARB)治疗。所有患者都接受临床评估(代谢状态、超声心动图、冠状动脉 CT 血管造影和心内膜心肌活检)。活检用于评估 ACE2、GlycACE2、Ang 1-9、Ang 1-7、MasR、NAFT 和纤维化。


不同受试者心肌细胞中的ACE2水平

与非T2DM心肌细胞相比,T2DM患者心肌细胞中的GlycACE2水平较高。此外,在T2DM患者心肌细胞中, Ang 1-9、Ang 1-7 和 MasR 的表达水平降低,表明 RAS 抑制在糖尿病心脏中的作用受损。因此,T2DM 受者的活检显示纤维化程度高于非 T2DM 受者。值得注意的是,心脏活检中 GlycACE2 的表达强烈依赖于血糖控制情况,这反映在12个月随访期间每季度评估的平均血浆 HbA1c 之间的相关性上。

总之,血糖控制不佳,会使GlycACE2水平升高,可能会减弱 RAS 抑制的心脏保护作用。但是,实现严格的血糖控制可使 RAS 抑制的抗重构作用正常化。

原始出处:

Marfella, R., D’Onofrio, N., Mansueto, G. et al. Glycated ACE2 reduces anti-remodeling effects of renin-angiotensin system inhibition in human diabetic hearts. Cardiovasc Diabetol 21, 146 (2022). https://doi.org/10.1186/s12933-022-01573-x

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    2023-01-14 docwu2019
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    2022-10-18 shanyongle
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    2023-06-28 quxin068
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    2022-08-08 屋顶瞄爱赏月

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