Glucagon-like peptide-1 (GLP-1) mediates cardioprotection by remote ischaemic conditioning.
Glucagon-like peptide-1 (GLP-1) mediates cardioprotection by remote ischaemic conditioning.
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DOI：
10.1093/cvr/cvw216
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发表时间：
2016-12
影响因子：
10.8
通讯作者：
Gourine A
中科院分区：
文献类型：
--
作者：
Basalay MV;Mastitskaya S;Mrochek A;Ackland GL;Del Arroyo AG;Sanchez J;Sjoquist PO;Pernow J;Gourine AV;Gourine A
尽管远端缺血适应(RIC)所建立的介导心脏保护的体液因子的性质尚不清楚，但副交感神经(迷走神经)机制似乎发挥了关键作用。由于许多胃肠激素的产生和释放是由迷走神经调节的，因此我们验证了RIC心脏保护是由胰高血糖素样肽-1(GLP-1)介导的假说。采用大鼠心肌梗死模型(冠状动脉结扎后再灌流)。在心肌缺血前或缺血期间阻断股动脉15分钟可诱导远端缺血预适应(RIPRE)或再适应(RIPER)。在切断颈迷走神经或膈下迷走神经的情况下，或在用特异性拮抗剂Exendin(9-39)阻断GLP-1受体(GLP-1R)后，测定RIPre和更成熟的心脏保护程度。检测PI3K/AKT和STAT3的磷酸化。RIPRE和RIPER使梗塞面积减少∼50%。在双侧颈部或膈下迷走神经切断术的情况下，RIPER未能建立心脏保护。阻断GLP-1R可阻断RIPRE或RIPER诱导的心肌保护作用。Exendin(9-39)也可抑制RIPre诱导的AKT磷酸化。切断颈迷走神经后，GLP-1R激动剂Exendin-4的心脏保护作用被保留，但在M3 M受体阻断的情况下，这种保护作用被取消。这些数据有力地表明，GLP-1作为一种体液因子发挥远程缺血条件下的心脏保护作用。这种现象需要内脏器官完整的迷走神经支配和GLP-1R介导的信号招募。GLP-1R激活诱导的心脏保护作用是通过M3 M受体介导的。
Although the nature of the humoral factor which mediates cardioprotection established by remote ischaemic conditioning (RIc) remains unknown, parasympathetic (vagal) mechanisms appear to play a critical role. As the production and release of many gut hormones is modulated by the vagus nerve, here we tested the hypothesis that RIc cardioprotection is mediated by the actions of glucagon-like peptide-1 (GLP-1). A rat model of myocardial infarction (coronary artery occlusion followed by reperfusion) was used. Remote ischaemic pre- (RIPre) or perconditioning (RIPer) was induced by 15 min occlusion of femoral arteries applied prior to or during the myocardial ischaemia. The degree of RIPre and RIPer cardioprotection was determined in conditions of cervical or subdiaphragmatic vagotomy, or following blockade of GLP-1 receptors (GLP-1R) using specific antagonist Exendin(9–39). Phosphorylation of PI3K/AKT and STAT3 was assessed. RIPre and RIPer reduced infarct size by ∼50%. In conditions of bilateral cervical or subdiaphragmatic vagotomy RIPer failed to establish cardioprotection. GLP-1R blockade abolished cardioprotection induced by either RIPre or RIPer. Exendin(9–39) also prevented RIPre-induced AKT phosphorylation. Cardioprotection induced by GLP-1R agonist Exendin-4 was preserved following cervical vagotomy, but was abolished in conditions of M3 muscarinic receptor blockade. These data strongly suggest that GLP-1 functions as a humoral factor of remote ischaemic conditioning cardioprotection. This phenomenon requires intact vagal innervation of the visceral organs and recruitment of GLP-1R-mediated signalling. Cardioprotection induced by GLP-1R activation is mediated by a mechanism involving M3 muscarinic receptors.
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影响因子：
3
作者：
Calvillo, Laura;Vanoli, Emilio;Schwartz, Peter J.
通讯作者：
Schwartz, Peter J.
影响因子：
3.7
作者：
Hibert P;Prunier-Mirebeau D;Beseme O;Chwastyniak M;Tamareille S;Lamon D;Furber A;Pinet F;Prunier F
通讯作者：
Prunier F
影响因子：
9.5
作者：
Davidson, Sean M.;Selvaraj, Pradeep;Yellon, Derek M.
通讯作者：
Yellon, Derek M.
影响因子：
7.7
作者：
Bose, AK;Mocanu, MM;Yellon, DM
通讯作者：
Yellon, DM
影响因子：
2.7
作者：
Basalay M;Barsukevich V;Mastitskaya S;Mrochek A;Pernow J;Sjöquist PO;Ackland GL;Gourine AV;Gourine A
通讯作者：
Gourine A