Loss of chondroitin sulfate proteoglycan sulfation allows delayed sympathetic reinnervation after cardiac ischemia-reperfusion.
Loss of chondroitin sulfate proteoglycan sulfation allows delayed sympathetic reinnervation after cardiac ischemia-reperfusion.
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DOI：
10.14814/phy2.15702
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发表时间：
2023-05
影响因子：
2.5
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中科院分区：
文献类型：
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心脏交感神经缺失可预测患者心肌梗死（MI）后室性心律失常的风险。心脏缺血-再灌注后交感神经去支配由心脏瘢痕中的基质成分硫酸软骨素蛋白聚糖（CSPGs）维持。我们发现CSPG的4，6-硫酸化对于防止神经生长到瘢痕中至关重要。用治疗方法促进早期神经再支配可减少MI后前2周内的心律失常，但恢复神经支配的长期后果尚不清楚。因此，我们询问早期神经再支配的有益效果是否持续。我们比较了在第3-10天用载体或用细胞内σ肽治疗以恢复神经支配的小鼠在MI后40天的心脏功能和心律失常易感性。令人惊讶的是，两组在MI后40天的心脏瘢痕中具有正常的神经支配密度，表明在媒介物处理的小鼠中梗死的延迟的神经再支配。这与两组的心功能和心律失常易感性相似相吻合。我们研究了心脏瘢痕延迟神经再支配的机制。我们发现，CSPG 4，6-硫酸化在缺血再灌注后早期升高，降低至对照水平，允许梗死的神经再支配。因此，损伤后数周细胞外基质的重塑导致心脏中交感神经元的重塑。
Sympathetic nerve loss in the heart predicts the risk of ventricular arrhythmias after myocardial infarction (MI) in patients. Sympathetic denervation after cardiac ischemia–reperfusion is sustained by matrix components chondroitin sulfate proteoglycans (CSPGs) in the cardiac scar. We showed that 4,6‐sulfation of CSPGs was critical for preventing nerve growth into the scar. Promoting early reinnervation with therapeutics reduces arrhythmias during the first 2 weeks after MI, but the longer‐term consequences of restoring innervation are unknown. Therefore, we asked if the beneficial effects of early reinnervation were sustained. We compared cardiac function and arrhythmia susceptibility 40 days after MI in mice treated on Days 3–10 with vehicle or with intracellular sigma peptide to restore innervation. Surprisingly, both groups had normal innervation density in the cardiac scar 40 days after MI, indicating delayed reinnervation of the infarct in vehicle‐treated mice. That coincided with similar cardiac function and arrhythmia susceptibility in the two groups. We investigated the mechanism allowing delayed reinnervation of the cardiac scar. We found that CSPG 4,6‐sulfation, which is elevated early after ischemia–reperfusion, was reduced to control levels allowing reinnervation of the infarct. Thus, remodeling of extracellular matrix weeks after injury leads to remodeling of sympathetic neurons in the heart.
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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：
7.3
作者：
Kilkenny, Carol;Browne, William;Altman, Douglas G.
通讯作者：
Altman, Douglas G.
影响因子：
20.1
作者：
Meloni M;Caporali A;Graiani G;Lagrasta C;Katare R;Van Linthout S;Spillmann F;Campesi I;Madeddu P;Quaini F;Emanueli C
通讯作者：
Emanueli C
影响因子：
9.7
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.
通讯作者：
Habecker, Beth A.
影响因子：
16.6
作者：
通讯作者：
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