Dynamin-related protein 1 as a therapeutic target in cardiac arrest.
Dynamin-related protein 1 as a therapeutic target in cardiac arrest.
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DOI：
10.1007/s00109-015-1257-3
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发表时间：
2015-03
影响因子：
4.7
通讯作者：
Sharp, Willard W.
中科院分区：
文献类型：
--
作者：
Sharp, Willard W.
尽管心肺复苏(CPR)的质量、除颤技术和治疗性低温的实施都有所改善，但院外心脏骤停(UchA)患者中，只有不到10%的人存活到出院。新的复苏疗法发展缓慢，部分原因是对复苏至关重要的病理生理机制尚不清楚。在心脏骤停期间，全身血流停止会导致全身缺血。CPR和恢复自主循环(ROSC)都会导致心脏的即刻再灌注损伤，其特征是严重的收缩功能障碍。与局部缺血/再灌注(IR)损伤(心肌梗死和卒中)不同，器官的整体IR损伤导致严重的器官功能障碍，缺血时间要短得多。心脏骤停复苏后最常见的两个受损器官--心脏和大脑--严重依赖线粒体功能。对线粒体动力学和线粒体分裂蛋白Dynamin相关蛋白1(Drp1)在细胞凋亡中的作用的新见解使靶向这些机制成为IR治疗的热点。在动物模型中，IR损伤或心脏骤停后抑制Drp1对心脏和大脑都有保护作用。本文就线粒体主要分裂蛋白Drp1与心脏缺血性改变的关系及其作为心脏骤停后新的治疗靶点进行了综述。
Despite improvements in cardiopulmonary resuscitation (CPR) quality, defibrillation technologies, and implementation of therapeutic hypothermia, less than 10% of out-of-hospital cardiac arrest (OHCA) victims survive to hospital discharge. New resuscitation therapies have been slow to develop, in part, because the pathophysiologic mechanisms critical for resuscitation are not understood. During cardiac arrest, systemic cessation of blood flow results in whole body ischemia. CPR, and the restoration of spontaneous circulation (ROSC), both result in immediate reperfusion injury of the heart that is characterized by severe contractile dysfunction. Unlike diseases of localized ischemia/reperfusion (IR) injury (myocardial infarction and stroke), global IR injury of organs results in profound organ dysfunction with far shorter ischemic times. The two most commonly injured organs following cardiac arrest resuscitation, the heart and brain, are critically dependent on mitochondrial function. New insights into mitochondrial dynamics and the role of the mitochondrial fission protein Dynamin-related protein 1 (Drp1) in apoptosis have made targeting these mechanisms attractive for IR therapy. In animal models, inhibiting Drp1 following IR injury or cardiac arrest confers protection to both the heart and brain. In this review, the relationship of the major mitochondrial fission protein Drp1 to ischemic changes in the heart and its targeting as a new therapeutic target following cardiac arrest are discussed.
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影响因子：
37.8
作者：
Go AS;Mozaffarian D;Roger VL;Benjamin EJ;Berry JD;Blaha MJ;Dai S;Ford ES;Fox CS;Franco S;Fullerton HJ;Gillespie C;Hailpern SM;Heit JA;Howard VJ;Huffman MD;Judd SE;Kissela BM;Kittner SJ;Lackland DT;Lichtman JH;Lisabeth LD;Mackey RH;Magid DJ;Marcus GM;Marelli A;Matchar DB;McGuire DK;Mohler ER 3rd;Moy CS;Mussolino ME;Neumar RW;Nichol G;Pandey DK;Paynter NP;Reeves MJ;Sorlie PD;Stein J;Towfighi A;Turan TN;Virani SS;Wong ND;Woo D;Turner MB;American Heart Association Statistics Committee and Stroke Statistics Subcommittee
通讯作者：
American Heart Association Statistics Committee and Stroke Statistics Subcommittee
影响因子：
37.8
作者：
Dezfulian C;Shiva S;Alekseyenko A;Pendyal A;Beiser DG;Munasinghe JP;Anderson SA;Chesley CF;Vanden Hoek TL;Gladwin MT
通讯作者：
Gladwin MT
影响因子：
4.8
作者：
Chang, Chuang-Rung;Manlandro, Cara Marie;Blackstone, Craig
通讯作者：
Blackstone, Craig
影响因子：
21.3
作者：
Bleazard, W;McCaffery, JM;Shaw, JM
通讯作者：
Shaw, JM
DOI：
10.3233/jad-2010-100552
发表时间：
2010
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Bossy B;Petrilli A;Klinglmayr E;Chen J;Lütz-Meindl U;Knott AB;Masliah E;Schwarzenbacher R;Bossy-Wetzel E
通讯作者：
Bossy-Wetzel E