Empagliflozin Improves the MicroRNA Signature of Endothelial Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Diabetes
Empagliflozin Improves the MicroRNA Signature of Endothelial Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction and Diabetes
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DOI：
10.1124/jpet.121.001251
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发表时间：
2023-01-01
影响因子：
3.5
通讯作者：
Santulli, Gaetano
中科院分区：
文献类型：
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作者：
Mone, Pasquale;Lombardi, Angela;Santulli, Gaetano
内皮功能障碍是射血分数保留性心力衰竭（HFpEF）、糖尿病（DM）和虚弱的关键机制。然而，缺乏可靠的生物标志物来监测这些患者的内皮功能障碍。在这项研究中，我们评价了一组参与调节HFpEF和DM患者人群内皮功能的循环microRNA（miR）的表达，这些患者接受恩格列净、二甲双胍或胰岛素治疗3个月。我们确定了一种独特的miR模式，与健康对照组和接受钠葡萄糖协同转运蛋白2（SGLT 2）抑制剂恩格列净治疗的HFpEF患者相比，HFpEF患者中的miR受到显著调节。与健康对照组相比，HFpEF患者中有三种miR显著下调（miR-126、miR-342- 3 p和miR-638），两种miR显著上调（miR-21和miR-92）。值得注意的是，HFpEF患者接受恩格列净治疗3个月后，其中两种miR（miR-21和miR-92）显著降低，而接受二甲双胍或胰岛素治疗的患者中未检测到内皮miR谱的显著差异。总之，我们的研究结果首次证明，参与内皮功能调节的特异性循环miR在虚弱的HFpEF DM患者中受到显著调节，并对SGLT 2抑制作出反应。
Endothelial dysfunction represents a key mechanism underlying heart failure with preserved ejection fraction (HFpEF), diabetes mellitus (DM), and frailty. However, reliable biomarkers to monitor endothelial dysfunction in these patients are lacking. In this study, we evaluated the expression of a panel of circulating microRNAs (miRs) involved in the regulation of endothelial function in a population of frail older adults with HFpEF and DM treated for 3 months with empagliflozin, metformin, or insulin. We identified a distinctive pattern of miRs that were significantly regulated in HFpEF patients compared to healthy controls and to HFpEF patients treated with the sodium glucose cotransporter 2 (SGLT2) inhibitor empagliflozin. Three miRs were significantly downregulated (miR-126, miR-342-3p, and miR-638) and two were significantly upregulated (miR-21 and miR-92) in HFpEF patients compared to healthy controls. Strikingly, two of these miRs (miR-21 and miR-92) were significantly reduced in HFpEF patients after the 3-month treatment with empagliflozin, whereas no significant differences in the profile of endothelial miRs were detected in patients treated with metformin or insulin. Taken together, our findings demonstrate for the first time that specific circulating miRs involved in the regulation of endothelial function are significantly regulated in frail HFpEF patients with DM and in response to SGLT2 inhibition.