Sodium-dependent glucose transporters (SGLT) in human ischemic heart: A new potential pharmacological target
Sodium-dependent glucose transporters (SGLT) in human ischemic heart: A new potential pharmacological target
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DOI：
10.1016/j.ijcard.2017.05.032
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发表时间：
2017-09-15
影响因子：
3.5
通讯作者：
Mannucci, Edoardo
中科院分区：
文献类型：
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作者：
Di Franco, Alessandra;Cantini, Giulia;Mannucci, Edoardo
背景资料：据报告，恩格列净可降低既往有心血管事件的2型糖尿病患者的心血管死亡率和心力衰竭住院率。这种钠/葡萄糖转运蛋白2（SGT 2）抑制剂的心脏作用机制尚未阐明，尽管可以假设药物对心肌细胞的直接作用。本研究的目的是评估SGLT 2和SGLT 1在正常、缺血和肥厚人类心脏中的相对表达，SGLT家族的两个最相关成员可能对恩格列净有反应。通过真实的时间定量RT-PCR分析健康（n = 9）、缺血（n = 9）和肥大（n = 6）人心脏的组织活检，共聚焦免疫荧光和Western印迹技术。我们发现SGLT 2在正常或病理条件下均不表达，而SGLT 1在正常心肌组织中表达，在缺血和肥大中显著上调，与细胞内第二信使AMP-活化蛋白激酶（AMPK）活化域的磷酸化增加相关，结论：这些发现开启了心肌细胞中高表达的SGLT 1可能代表心脏保护的潜在药理学靶点的可能性。(C)2017爱思唯尔B. V.保留所有权利。
Background: Empagliflozin is reported to reduce cardiovascular mortality and the rate of hospitalization for heart failure in type 2 diabetic patients with prior cardiovascular events. The mechanisms underlying the cardiac effects of this sodium/glucose transporter 2 (SGT2) inhibitor have not yet been clarified, though a direct action of the drug on the cardiomyocytes could be hypothesized. The aim of the present study is to assess the relative expression of SGLT2 and SGLT1, the two most relevant members of the SGLT family being potentially responsive to empagliflozin, in normal, ischemic and hypertrophic human hearts.Methods: Tissue biopsies of healthy (n = 9), ischemic (n = 9) and hypertrophic (n = 6) human hearts were analyzed by real time quantitative RT-PCR, confocal immunofluorescence and Western blot techniques.Results: We found no expression of SGLT2 in either normal or pathological conditions, whereas SGLT1 was expressed in normal myocardial tissue and significantly upregulated in ischemia and hypertrophy, in association with increased phosphorylation in activating domains of the intracellular second messengers AMP-activated protein kinase (AMPK), extracellular-signal regulated kinase 1 and 2 (ERK-1/2) and mammalian target of rapamycin (mTOR).Conclusions: These findings open the possibility that hyperexpressed SGLT1 in cardiomyocytes may represent a potential pharmacological target for cardioprotection. (C) 2017 Elsevier B.V. All rights reserved.