In the heart, the sodium channel Na_V1.5 is essential for proper electrical conductivity. Indeed, diminished Na_V1.5 function has been associated with conduction slowing, arrhythmia and sudden cardiac death. The channel resides in the cardiomyocyte membrane, being particularly enriched at intercalated discs—connection points between the cells—but how it gets there is unclear. Because trafficking of proteins generally depends on the microtubule network and because the microtubule protein EB1 is enriched at intercalated discs, Marchal and colleagues investigated EB1’s role in Na_V1.5 localization. They show that over-expression of EB1 in human cardiomyocytes (derived from stem cells) increased the membrane localization of Na_V1.5 as well as the sodium current velocity of these cells, while knock-down of EB1 in these cells, or in the hearts of zebrafish, significantly reduced sodium current velocities. Furthermore, stabilization of microtubules—via treatment with a compound called SB2—increased both sodium current velocity and the density of Na_V1.5 at intercalated discs in mouse cardiomyocytes. The results not only uncover EB1’s role in Na_V1.5 localization, but suggest microtubule modulation as a possible way to compensate for diminished Na_V1.5 function in certain arrhythmias.

Following a myocardial infarction, inflammation and fibrosis of the heart can cause it to eventually fail. To provide prognoses in such cases of ischemic heart failure, doctors often use imaging techniques such as positron emission tomography (PET) and cardiac magnetic resonance (CMR) to measure the extent of inflammation and fibrosis. Whether such imaging is of value for non-ischemic heart failure remains unclear, however. To find out, Glaseneap and colleagues performed transverse aortic constriction (TAC) on mice—to model non-ischemic heart failure—and then analyzed the animals’ hearts with PET (using a inflammation-specific tracer) and CMR (to measure scar tissue). Compared with sham-operated animals, those that underwent TAC exhibited increased heart inflammation for at least three weeks and significant fibrosis for at least six weeks, the team showed. And, the degree of scarring and inflammation was inversely correlated with heart function. Lastly, the team reported that reversal of TAC led to reduced inflammation and fibrosis over time. Together the results confirm that PET and CMR are valuable for monitoring fibrosis and inflammation in non-ischemic heart failure and could potentially be used for assessing the effectiveness of interventions.

After a myocardial infarction, restoring blood flow is essential to saving muscle function, but it also causes a degree of damage due to inflammation and cell death—so called reperfusion injury. Shi and colleagues now show that much of this cell death occurs via pyroptosis—a controlled form of necrosis involving excessive inflammatory factor release. The team found that cultured cardiomyocytes, when starved of oxygen and then resupplied with the gas, exhibited features of pyroptosis including the release of inflammatory factors, increased production of the pyroptotic factor gasdermin D and death. Cardiomyocytes lacking gasdermin D, by contrast, did not display signs of pyroptosis under these conditions. The team went on to show that gasdemin D was significantly increased in the hearts of mice following ischemia/reperfusion. And that, compared with control animals, mice whose cardiomyocytes were engineered to lack gasdermin D suffered less necrosis and smaller reperfusion injuries in their hearts. There was no difference in the proportion of apoptosis in the hearts of these test and control animals. Together the findings may offer insights into ways to minimize pyroptosis and thus ischemia/reperfusion injury following myocardial infarctions, say the authors.

在心脏中，钠通道 Na _V 1.5 对于适当的导电性至关重要。事实上，Na _V 1.5 功能减弱与传导减慢、心律失常和心源性猝死有关。该通道位于心肌细胞膜中，在插入的椎间盘（细胞之间的连接点）处特别丰富，但尚不清楚它是如何到达那里的。由于蛋白质的运输通常取决于微管网络，并且微管蛋白质 EB1 在插入的椎间盘中富集，因此 Marchal 及其同事研究了 EB1 在 Na _V 1.5 定位中的作用。他们表明 EB1 在人心肌细胞（源自干细胞）中的过度表达增加了 Na _V的膜定位1.5 以及这些细胞的钠电流速度，同时敲低这些细胞或斑马鱼心脏中的 EB1，显着降低钠电流速度。此外，通过用一种叫做 SB2 的化合物处理微管的稳定性增加了钠电流速度和小鼠心肌细胞插入椎间盘的 Na _V 1.5密度。结果不仅揭示了 EB1 在 Na _V 1.5 定位中的作用，而且表明微管调节可作为补偿某些心律失常中减弱的 Na _V 1.5 功能的一种可能方式。

心肌梗塞后，心脏的炎症和纤维化可导致其最终衰竭。为了在这种缺血性心力衰竭病例中提供预后，医生经常使用成像技术，如正电子发射断层扫描 (PET) 和心脏磁共振 (CMR) 来测量炎症和纤维化的程度。然而，这种成像是否对非缺血性心力衰竭有价值仍不清楚。为了找到答案，Glaseneap 及其同事对小鼠进行了横向主动脉缩窄 (TAC)——以模拟非缺血性心力衰竭——然后用 PET（使用炎症特异性示踪剂）和 CMR（测量疤痕组织）分析动物的心脏. 与假手术动物相比，那些接受 TAC 的动物表现出至少三周的心脏炎症增加和至少六周的显着纤维化，团队展示了。而且，疤痕和炎症的程度与心脏功能呈负相关。最后，该团队报告说，随着时间的推移，TAC 的逆转导致炎症和纤维化减少。结果共同证实，PET 和 CMR 对监测非缺血性心力衰竭的纤维化和炎症很有价值，并且有可能用于评估干预措施的有效性。

心肌梗塞后，恢复血流对于挽救肌肉功能至关重要，但它也会因炎症和细胞死亡而造成一定程度的损伤，即所谓的再灌注损伤。Shi及其同事现在表明，这种细胞死亡大部分是通过细胞焦亡发生的——一种涉及过度炎症因子释放的受控坏死形式。研究小组发现，培养的心肌细胞在缺氧后重新补充气体时，会表现出细胞焦亡的特征，包括炎症因子的释放、焦亡因子 gasdermin D 的产生增加和死亡。相比之下，缺乏gasdermin D的心肌细胞在这些条件下没有表现出细胞焦亡的迹象。该团队继续表明，缺血/再灌注后小鼠心脏中的gasdemin D显着增加。然后，与对照动物相比，心肌细胞被设计为缺乏 gasdermin D 的小鼠的心脏坏死较少，再灌注损伤较小。在这些测试和对照动物的心脏中，细胞凋亡的比例没有差异。这组作者说，这些发现可能共同为减少心肌梗死后细胞焦亡和缺血/再灌注损伤的方法提供见解。