Therapeutics That Promote Sympathetic Reinnervation Modulate the Inflammatory Response After Myocardial Infarction.
Therapeutics That Promote Sympathetic Reinnervation Modulate the Inflammatory Response After Myocardial Infarction.
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促进交感神经再支配的治疗方法可调节心肌梗死后的炎症反应。
DOI：
10.1016/j.jacbts.2022.04.009
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发表时间：
2022-09
影响因子：
9.7
通讯作者：
Habecker, Beth A.
中科院分区：
文献类型：
--
作者：
Sepe, Joseph J.;Gardner, Ryan T.;Blake, Matthew R.;Brooks, Deja M.;Staffenson, Melanie A.;Betts, Courtney B.;Sivagnanam, Sam;Larson, William;Kumar, Sushil;Bayles, Richard G.;Jin, Haihong;Cohen, Michael S.;Coussens, Lisa M.;Habecker, Beth A.
采用23种抗体的定量多重免疫组织化学用于鉴定缺血再灌注后2周左心室中存在的免疫细胞。两种治疗剂（ISP和HJ-02），在缺血-再灌注后第3-10天给药，恢复了整个左心室的交感神经支配，降低了心律失常的易感性。ISP和HJ-02治疗使免疫反应从炎症性转变为修复性，在再神经支配的心脏中，促炎性（M1样）巨噬细胞减少，调节性T细胞和修复性（M2样）巨噬细胞数量增加。与ISP相比，HJ-02刺激了从促炎性细胞类型到修复性细胞类型的显著更大的转变，这与梗死面积减小和正常心输出量和射血分数一致。ISP和HJ-02都没有改变培养的腹腔巨噬细胞中的巨噬细胞表型，这表明神经再支配有助于体内M1向M2的转变。心肌梗死（MI）引发炎症反应，随着时间的推移，炎症反应从促炎性转变为修复性。心肌梗死后恢复心脏交感神经可预防心律失常。这项研究调查了神经再支配是否改变了MI后的免疫反应。本研究使用定量多重免疫组织化学来鉴定缺血再灌注后2周心脏中存在的免疫细胞。两种疗法刺激神经再支配，防止心律失常，并将免疫反应从炎症性转移到修复性，具有更少的促炎性巨噬细胞和更多的调节性T细胞和修复性巨噬细胞。在体外，治疗没有改变巨噬细胞表型，这表明神经再支配有助于改变免疫应答。
Quantitative multiplex immunohistochemistry employing 23 antibodies was used to identify the immune cells present in the left ventricle 2 weeks after ischemia-reperfusion. Two therapeutics (ISP and HJ-02), administered on days 3-10 after ischemia-reperfusion, restored sympathetic innervation throughout the left ventricle and decreased arrhythmia susceptibility. Treatment with ISP and HJ-02 shifted the immune response from inflammatory to reparative, with fewer pro-inflammatory (M1-like) macrophages and increased numbers of regulatory T cells and reparative (M2-like) macrophages in reinnervated hearts. HJ-02 stimulated a significantly greater shift from pro-inflammatory to reparative cell types compared with ISP, which coincided with decreased infarct size and normal cardiac output and ejection fraction. Neither ISP nor HJ-02 altered macrophage phenotypes in cultured peritoneal macrophages, which suggested that reinnervation contributes to the M1 to M2 shift in vivo. Myocardial infarction (MI) triggers an inflammatory response that transitions from pro-inflammatory to reparative over time. Restoring sympathetic nerves in the heart after MI prevents arrhythmias. This study investigated if reinnervation altered the immune response after MI. This study used quantitative multiplex immunohistochemistry to identify the immune cells present in the heart 2 weeks after ischemia-reperfusion. Two therapeutics stimulated reinnervation, preventing arrhythmias and shifting the immune response from inflammatory to reparative, with fewer pro-inflammatory macrophages and more regulatory T cells and reparative macrophages. Treatments did not alter macrophage phenotype in vitro, which suggested reinnervation contributed to the altered immune response.
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影响因子：
9.3
作者：
Dyck S;Kataria H;Alizadeh A;Santhosh KT;Lang B;Silver J;Karimi-Abdolrezaee S
通讯作者：
Karimi-Abdolrezaee S
影响因子：
16.6
作者：
Buscher K;Ehinger E;Gupta P;Pramod AB;Wolf D;Tweet G;Pan C;Mills CD;Lusis AJ;Ley K
通讯作者：
Ley K
影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
DOI：
10.1136/heartjnl-2015-307855
发表时间：
2016-03
期刊：
Heart (British Cardiac Society)
影响因子：
--
作者：
Bulluck H;Yellon DM;Hausenloy DJ
通讯作者：
Hausenloy DJ
影响因子：
20.1
作者：
Nahrendorf M;Swirski FK
通讯作者：
Swirski FK