Cardiomyocytes derived from human pluripotent stem cells (hPSC) are a valuable resource for drug discovery, disease modeling, and more. But, generally speaking, such cells remain immature compared with their natural adult counterparts, limiting their use. A variety of methods exist to promote maturation, but there is currently no consensus on the best way to assess such maturity—some researchers use electrophysiology, others transcriptome data and so on. Cai and colleagues have, therefore, established a straightforward, yet comprehensive, mass spectrometry approach. The method combines analysis of a subset of intact proteins with an unbiased screen of digested peptide fragments. The team used the method to examine early and late-stage maturation of cardiomyocytes derived from embryonic and induced hPSCs, validating their findings against cells from mouse hearts. For the intact protein analysis, sarcomeres were isolated from cell samples, allowing identification of the major sarcomeric proteins and their maturation-related post-translational modifications, while the unbiased screen enabled identification of both known and novel maturation markers. The work, thus, not only provides a handy tool for assessing maturity, but also a set of maturity markers for cross-reference.

Natriuretic peptide (NP) is a hormone that promotes sodium excretion via the urine as well as other physiological effects. It is secreted from the heart’s atrial cardiac muscle, and low levels of NP are associated with risk of cardiometabolic diseases, including hypertension and diabetes. Being black is also a risk factor for such conditions, and a study of middle-aged and older people revealed that blacks tend to have lower NP levels than whites. Whether this difference is apparent in young healthy individuals before such diseases emerge, however, was unknown. To find out, Patel et al examined the levels of NP and factors that regulate the hormone in a cohort of young adults, half of whom were black. The team showed that, on average, blacks had significantly lower levels of NP and higher levels of factors that downregulate the hormone than whites. Analysis of heart tissue collected from deceased organ donors also revealed that proteins involved in the processing and clearance of NP tended to be more abundant in black individuals. The results sow the seeds for future investigations into whether NP levels directly influence cardiometabolic disease, and if so, whether interventions to boost the hormone could be of clinical benefit.

Leptin—a hormone released from fatty tissue—increases metabolism and blood pressure and reduces appetite. In obese individuals, however, despite high levels of leptin, metabolism and appetite may be unaltered, yet hypertension may still develop. Leptin’s effects on appetite and metabolism are mediated in the brain, while its effects on blood pressure are thought to be mediated elsewhere. Indeed, Shin and colleagues suspected the carotid body (CB)—a cluster of cells in the neck that detect blood levels of oxygen and other substances and communicate the information to the brain via the carotid sinus nerve (CSN). The CB has abundant expression of a leptin receptor and, moreover, leptin has been shown to increase CSN firing. Shin and colleagues now show that, indeed, infusions of leptin into mice increased hypertension in the animals only when the CSN was intact. They also showed that this effect was dependent on the ion channel Trpm7, which is abundant in the CB. Furthermore, inhibition of Trpm7 prevented the leptin-induced hypertension. Together, the results begin to explain why, in obese individuals, leptin still induces hypertension when the hormone’s other effects are diminished. And they suggest that inhibition of Trpm7 could be a way to treat hypertension, particularly in obese individuals.

源自人多能干细胞（hPSC）的心肌细胞是用于药物发现，疾病建模等的宝贵资源。但是，一般而言，此类细胞与其天然的成年细胞相比仍不成熟，限制了它们的使用。存在多种促进成熟的方法，但是目前尚无关于评估这种成熟度的最佳方法的共识-一些研究人员使用电生理学，而另一些转录组数据等等。因此，蔡和同事建立了一种简单而全面的质谱方法。该方法结合了完整蛋白子集的分析和无偏见消化的肽片段的筛选。研究小组使用该方法检查了源自胚胎和诱导的hPSC的心肌细胞的早期和晚期成熟，验证他们针对老鼠心脏细胞的发现。为了进行完整的蛋白质分析，从细胞样品中分离了肉瘤，从而可以鉴定主要的肌节蛋白及其成熟相关的翻译后修饰，而无偏筛选可以鉴定已知和新型成熟标记。因此，这项工作不仅为评估成熟度提供了方便的工具，而且为交叉参考提供了一组成熟度标记。

利钠肽（NP）是一种激素，可通过尿液促进钠排泄以及其他生理作用。它是从心脏的心房心肌中分泌出来的，而低水平的NP与心脏代谢疾病（包括高血压和糖尿病）的风险有关。黑人也是此类疾病的危险因素，对中老年人的研究表明，黑人的NP水平往往低于白人。然而，这种差异在这种疾病出现之前是否在年轻健康的个体中是否明显是未知的。为了找出答案，Patel等人在一群年轻人（其中一半是黑人）中检查了NP的水平和调节激素的因子。研究小组表明，与白人相比，黑人平均具有较低的NP水平和下调激素水平的较高水平的因子。从死者器官供体收集的心脏组织的分析还显示，黑人个体中参与NP加工和清除的蛋白质往往更为丰富。该结果为将来研究NP水平是否直接影响心脏代谢疾病以及是否进行干预以增强激素的干预是否具有临床价值奠定了基础。

瘦素（一种从脂肪组织释放的激素）会增加新陈代谢和血压，并降低食欲。然而，在肥胖的个体中，尽管瘦素水平很高，但其代谢和食欲可能并没有改变，但高血压仍可能发展。瘦素对食欲和代谢的影响在大脑中被介导，而其对血压的影响被认为在其他地方被介导。确实，Shin和他的同事怀疑颈动脉体（CB）—脖子上的一簇细胞，可检测血液中的氧气和其他物质的水平，并通过颈窦神经（CSN）将信息传递给大脑。CB具有瘦素受体的丰富表达，此外，瘦素已显示出可增强CSN放电。Shin和他的同事现在表明，的确，仅当CSN完好无损时，向小鼠中注入瘦蛋白才会增加动物的高血压。他们还表明，这种效应取决于离子通道Trpm7，该通道在CB中含量丰富。此外，抑制Trpm7可以预防瘦素诱导的高血压。在一起，结果开始解释为什么在肥胖个体中，当荷尔蒙的其他作用减弱时，瘦素仍会诱发高血压。他们认为抑制Trpm7可能是治疗高血压的一种方法，特别是在肥胖人群中。当激素的其他作用减弱时，瘦素仍会诱发高血压。他们认为抑制Trpm7可能是治疗高血压的一种方法，特别是在肥胖人群中。当激素的其他作用减弱时，瘦素仍会诱发高血压。他们认为抑制Trpm7可能是治疗高血压的一种方法，特别是在肥胖人群中。