Spinal cord astrocytes regulate myocardial ischemia-reperfusion injury.
Spinal cord astrocytes regulate myocardial ischemia-reperfusion injury.
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DOI：
10.1007/s00395-022-00968-x
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发表时间：
2022-11-11
影响因子：
9.5
通讯作者：
He S
中科院分区：
文献类型：
--
作者：
Wu C;Liu R;Luo Z;Sun M;Qile M;Xu S;Jin S;Zhang L;Gross ER;Zhang Y;He S
星形胶质细胞在对损伤和伤害性刺激的反应中起关键作用，但其在心肌缺血再灌注（I/R）损伤中的作用仍不清楚。在这里，我们确定是否操纵脊髓星形胶质细胞活性影响心肌I/R损伤和潜在的机制。通过结扎大鼠左冠状动脉建立在体I/R模型，观察到心肌I/R损伤后脊髓胶质细胞酸性蛋白（GFAP）蛋白水平升高1.7倍。鞘内注射氟柠檬酸盐（一种星形胶质细胞抑制剂）抑制脊髓星形胶质细胞，可降低GFAP免疫染色，并使梗死面积相对于I/R组减少29%。使用由设计药物专门激活的设计受体（DREADD）化学遗传学方法，我们采用GFAP启动子驱动的Gq-或Gi-偶联信号传导双向操纵星形胶质细胞活性。Gq-DREADD介导的脊髓星形胶质细胞激活引起瞬时受体电位香草酸1（TRPV 1）激活和神经肽释放，导致梗死面积增加1.3倍，血清去甲肾上腺素水平升高1.2倍，心律失常评分高于I/R组。相反，Gi-DREADD介导的脊髓星形胶质细胞抑制TRPV 1介导的伤害性信号传导，导致I/R组梗死面积减少35%，心律失常评分减少51%，血清去甲肾上腺素水平从3158 ± 108降至2047 ± 95 pg/mL。此外，鞘内注射TRPV 1或神经肽拮抗剂可减少梗死面积和血清去甲肾上腺素水平。这些发现表明脊髓星形胶质细胞在心肌I/R损伤中的功能作用，并提供了一种新的潜在的治疗方法，针对脊髓星形胶质细胞预防心脏损伤。
Astrocytes play a key role in the response to injury and noxious stimuli, but its role in myocardial ischemia–reperfusion (I/R) injury remains largely unknown. Here we determined whether manipulation of spinal astrocyte activity affected myocardial I/R injury and the underlying mechanisms. By ligating the left coronary artery to establish an in vivo I/R rat model, we observed a 1.7-fold rise in glial fibrillary acidic protein (GFAP) protein level in spinal cord following myocardial I/R injury. Inhibition of spinal astrocytes by intrathecal injection of fluoro-citrate, an astrocyte inhibitor, decreased GFAP immunostaining and reduced infarct size by 29% relative to the I/R group. Using a Designer Receptor Exclusively Activated by Designer Drugs (DREADD) chemogenetic approach, we bi-directionally manipulated astrocyte activity employing GFAP promoter-driven Gq- or Gi-coupled signaling. The Gq-DREADD-mediated activation of spinal astrocytes caused transient receptor potential vanilloid 1 (TRPV1) activation and neuropeptide release leading to a 1.3-fold increase in infarct size, 1.2-fold rise in serum norepinephrine level and higher arrhythmia score relative to I/R group. In contrast, Gi-DREADD-mediated inhibition of spinal astrocytes suppressed TRPV1-mediated nociceptive signaling, resulting in 35% reduction of infarct size and 51% reduction of arrhythmia score from I/R group, as well as lowering serum norepinephrine level from 3158 ± 108 to 2047 ± 95 pg/mL. Further, intrathecal administration of TRPV1 or neuropeptide antagonists reduced infarct size and serum norepinephrine level. These findings demonstrate a functional role of spinal astrocytes in myocardial I/R injury and provide a novel potential therapeutic approach targeting spinal cord astrocytes for the prevention of cardiac injury.
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脊髓刺激通过减少反应性神经胶质和脊柱中间神经元的激活来减少心室心律不齐。
DOI：
10.1016/j.jacep.2021.05.016
发表时间：
2021-10
期刊：
JACC. Clinical electrophysiology
影响因子：
--
作者：
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Mahajan A
DOI：
10.3390/molecules27031031
发表时间：
2022-02-03
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Castrejón-Téllez V;Del Valle-Mondragón L;Pérez-Torres I;Guarner-Lans V;Pastelín-Hernández G;Ruiz-Ramírez A;Díaz-Juárez JA;Varela-López E;Oidor-Chan VH;Vargas-González A;Martínez-Memije R;Flores-Chávez P;León-Ruíz B;Arriaga-Carrillo S;Torres-Narváez JC
通讯作者：
Torres-Narváez JC
影响因子：
5.5
作者：
Domingues HS;Portugal CC;Socodato R;Relvas JB
通讯作者：
Relvas JB
影响因子：
9.5
作者：
Gross ER;Hsu AK;Urban TJ;Mochly-Rosen D;Gross GJ
通讯作者：
Gross GJ
影响因子：
9.5
作者：
Davidson SM;Arjun S;Basalay MV;Bell RM;Bromage DI;Bøtker HE;Carr RD;Cunningham J;Ghosh AK;Heusch G;Ibanez B;Kleinbongard P;Lecour S;Maddock H;Ovize M;Walker M;Wiart M;Yellon DM
通讯作者：
Yellon DM