Evidence suggests that T cells are involved in hypertension. Indeed, many stimuli that induce hypertension, including angiotensin II, high salt, and stress, also activate T cells. Once the stimulus abates, most of these cells will die, but a small number may go on to form memory T cells, which reside long-term in bone marrow and can be reactivated if the stimulus returns. Because hypertension increases sympathetic tone, and because sympathetic nerves entering the bone marrow modulate blood cell production, Xiao and colleagues hypothesized that these bone marrow neurons might drive accumulation and activation of hypertension-specific memory T cells. They showed that, compared with control mice, those with denervated bone marrow had reduced homing and proliferation of memory T cells in response to hypertensive stimuli. And that stimulation of sympathetic nerve activity increased bone marrow accumulation of such cells. The team also showed that β2 adrenergic signaling mediated this memory cell accumulation and that blockade of β2 receptors protected mice from repeated hypertensive stimuli. The results highlight bone marrow sympathetic neurons as a new target for hypertension treatments and suggest β blockers as one possible way to inhibit them.

Healthy heart cells primarily use fatty acids for their metabolism but can also use carbohydrates and amino acids as fuel sources, if required. In many heart diseases, this typical metabolic profile is altered. For example, in cardiac hypertrophy, the cells switch to metabolizing mainly glucose, while in type II diabetes, they become fixed on fatty acid metabolism with a greatly limited ability to switch fuels. Currently, there are no well-established methods for noninvasively examining such metabolic alterations in patients. However, a recently developed imaging technique called hyperpolarized ¹³C magnetic resonance imaging (MRI) offers the potential to do just that. Rider and colleagues are now the first investigators to use the technique to examine heart metabolism in patients with type II diabetes. They show that while carbohydrate metabolism—as measured by conversion of ¹³C- pyruvate to other metabolites—did increase in both patients and healthy controls after consuming a glucose drink, carbohydrate metabolism during fasting was distinctly lower in patients than controls, in line with earlier findings. This proof-of-principle study now lays the groundwork for using hyperpolarized ¹³C MRI in patients with a range of heart diseases.

cMyBP-C (cardiac myosin-binding protein-C) is a sarcomeric protein necessary for normal heart contractions and for the increased contractility seen during fight-or-flight responses. Exactly how cMyBP-C controls sarcomere dynamics, however, is only partially understood. One problem is that truncated versions of cMyBP-C used for in vitro functional studies fail to localize correctly—because localization requires the missing C terminus. Napierski and colleagues’ new method circumvents this issue. They use an engineered cMyBP-C that contains a specific enzyme cleavage site and tag site (called SpyTag). The protein first localizes normally to sarcomeres and is then cleaved to release the N terminus leaving the SpyTag exposed. A replacement N terminus containing a SpyCatcher sequence then covalently fuses with the SpyTag to form a new cMyBP-C. Using this approach, the team showed that loss of the N-terminus led to spontaneous oscillatory contractions of sarcomeres and that replacement with an unphosphorylated N terminus, but not a phosphorylated version, dramatically dampened these oscillations. The work reveals a new role for cMyBP-C in regulating contractile oscillations and highlights the utility of the cut-and-paste technique for studying cMyBP-C and potentially other proteins.

有证据表明T细胞参与了高血压。实际上，许多诱发高血压的刺激，包括血管紧张素II，高盐和压力，也能激活T细胞。一旦刺激减弱，这些细胞中的大多数将死亡，但少数细胞可能继续形成记忆T细胞，这些细胞长期存在于骨髓中，如果刺激恢复，则可以重新激活。由于高血压会增加交感神经张力，并且由于进入骨髓的交感神经会调节血细胞的生成，Xiao及其同事假设这些骨髓神经元可能会驱动高血压特异性记忆T细胞的积累和激活。他们显示，与对照组小鼠相比，患有失神经骨髓的小鼠对高血压刺激的记忆T细胞的归巢和增殖减少。刺激交感神经活动会增加此类细胞的骨髓积累。该研究小组还表明，β2肾上腺素能信号传导介导了这种记忆细胞的蓄积，β2受体的阻滞保护了小鼠免受反复的高血压刺激。该结果突出了骨髓交感神经元作为高血压治疗的新靶标，并提出了β受体阻滞剂作为抑制它们的一种可能方法。

健康的心脏细胞主要使用脂肪酸进行新陈代谢，但如果需要，也可以使用碳水化合物和氨基酸作为燃料来源。在许多心脏病中，这种典型的新陈代谢模式被改变。例如，在心脏肥大中，细胞转变为主要代谢葡萄糖，而在II型糖尿病中，它们被固定在脂肪酸代谢上，而转换燃料的能力非常有限。目前，尚无成熟的方法可以无创地检查患者的这种代谢变化。但是，最近开发的成像技术称为超极化¹³C磁共振成像（MRI）提供了实现此目的的潜力。现在，Rider及其同事是第一批使用该技术检查II型糖尿病患者心脏代谢的研究者。他们表明，尽管碳水化合物代谢（通过¹³ C-丙酮酸转化为其他代谢物进行测量）在饮用葡萄糖饮料后在患者和健康对照组中均增加了，但空腹期间患者的碳水化合物代谢明显低于对照组，这与早期发现。现在，这项原理验证研究为在患有多种心脏病的患者中使用超极化¹³ C MRI奠定了基础。

cMyBP-C（心肌肌球蛋白结合蛋白-C）是正常心脏收缩和战斗或逃跑反应中所见收缩力增加所必需的肌节蛋白。但是，仅部分了解了cMyBP-C如何控制肌节动力学。一个问题是用于体外功能研究的cMyBP-C的截短版本无法正确定位-因为定位需要缺少C末端。Napierski和同事的新方法规避了这个问题。他们使用经过工程改造的cMyBP-C，其中包含特定的酶切割位点和标签位点（称为SpyTag）。该蛋白质首先正常定位于肉瘤，然后被切割以释放N末端，从而使SpyTag暴露。然后，包含SpyCatcher序列的替换N末端与SpyTag共价融合，形成一个新的cMyBP-C。研究小组使用这种方法表明，N末端的缺失会导致肉瘤的自发振荡收缩，而用未磷酸化的N末端（而不是磷酸化的末端）替换会大大减弱这些振荡。这项工作揭示了cMyBP-C在调节收缩振荡中的新作​​用，并强调了剪切粘贴技术在研究cMyBP-C和其他潜在蛋白质方面的实用性。