In normal healthy hearts, the aorta and pulmonary arteries arise from the left and right ventricles, respectively. But in transposition of the great arteries (TGA), a common developmental heart malformation, the plumbing of these two major vessels is switched. The genetic etiology of this life-threatening condition, which requires surgery in the early days of life, is largely unknown. Liu and colleagues thus examined the whole-exome sequences of 249 TGA patients and, in 66 cases, their parents in the hopes of finding genetic clues. The analysis yielded 82 candidate genes, in which variants or mutations present in TGA patients were likely to alter protein function. And, of these, almost a quarter (19) were involved in cilia function. TGA has been hypothesized to arise from disturbances in left-right patterning during embryo development. And cilia are essential for left-right axis determination—through their control of morphogen flow, among other things. Cilia genes have also been implicated in some other congenital heart malformations. The findings of Liu and colleagues not only provide insights into the etiology of this hitherto mysterious malformation, but may also inform future prenatal diagnostic tests for the condition, say the authors.

High levels of lipids in the blood increase a person’s risk of cardiovascular disease (CVD). And evidence suggests this risk builds over a lifetime. But, for young adults, data on lipid levels and CVD risk is limited. Park and colleagues, therefore, examined health data for close to 2 million Korean individuals aged 20 to 39, none of whom had ever been treated for high cholesterol (with statins), or suffered myocardial infarctions (MI) or strokes. Over a 4-year period, the subjects had undergone at least 3 lipid measurements as part of health assessments and were then followed for a further 4 years or until death. The data showed that high baseline lipid levels were linked with increased risk of adverse cardiovascular events, in particular MI. They also showed that subjects who exhibited high variability in lipid level measurements were not at greater risk of such events. Such ups and downs have previously been linked to CVD, but Park and colleagues argue that statin use in other cohorts may contribute to variability and confound interpretation—an issue their study avoids. Together, the results indicate that lipid levels in young adults can indeed indicate future CVD risk and, therefore, suggest lipid-lowering strategies could be of benefit for this age group.

Hypertension is prevalent in the world’s adult population and is a major risk factor for heart disease and stroke. A high-salt diet (HSD) can drive hypertension, but complete details about how salt intake shapes pathology are lacking. Recent studies show that fecal transfer from hypertensive to normotensive animals can lead to hypertension in the recipients, suggesting gut flora plays a role. Now, Yan and colleagues show that rats on an HSD have altered gut flora profiles and, in particular, that the abundance of Bacteroides fragilis is reduced. Analysis of intestinal metabolites and substances in HSD-fed rats also revealed that levels of arachidonic acid (AA)—produced by B fragilis—were low, and levels of the stress hormone corticosterone, which regulates blood pressure, were raised. The team went on to show that supernatants from B fragilis cultures could prevent corticosterone production in intestinal tissue of HSD-fed mice, as could treatment with AA. Moreover, both B fragilis and AA were found to be lower in the feces of humans with hypertension than that of healthy controls. The results suggest B fragilis and AA normally curb corticosterone production and could, therefore, be novel targets for hypertension treatment strategies.

在正常健康的心脏中，主动脉和肺动脉分别来自左心室和右心室。但是在大动脉（TGA）（一种常见的发育性心脏畸形）的移位中，这两个主要血管的管道被切换了。这种威胁生命的疾病的遗传病因在生命的早期需要进行手术，目前尚不清楚。因此，Liu和他的同事检查了249位TGA患者的全外显子序列，以及66位患者的父母，以期寻找遗传线索。该分析产生了82个候选基因，其中TGA患者中存在的变异或突变可能会改变蛋白质功能。其中，将近四分之一（19）与纤毛功能有关。据推测，TGA是由胚胎发育过程中左右构图的紊乱引起的。纤毛对于左右轴的确定至关重要，尤其是通过它们控制形态发生子的流动。纤毛基因也与其他一些先天性心脏畸形有关。这组作者说，Liu及其同事的发现不仅提供了对迄今这种神秘畸形的病因学的见解，而且还可能为该病的未来产前诊断测试提供了信息。

血液中高水平的脂质会增加人患心血管疾病（CVD）的风险。有证据表明，这种风险是一生中累积的。但是，对于年轻人，有关脂质水平和CVD风险的数据有限。因此，Park及其同事检查了近200万韩国人的健康数据，这些人年龄在20至39岁之间，他们中的任何人都没有接受过高胆固醇（他汀类药物）的治疗，心肌梗塞（MI）或中风。在4年的时间里，作为健康评估的一部分，对受试者进行了至少3次脂质测量，然后再随访4年或直至死亡。数据显示，高基线血脂水平与不良心血管事件（尤其是心梗）的风险增加相关。他们还表明，在脂质水平测量中表现出高度变异性的受试者没有发生此类事件的更大风险。这种起伏以前曾与CVD相关，但是Park及其同事认为，其他人群中他汀类药物的使用可能会导致变异性和解释混乱，这是他们的研究避免的问题。总之，结果表明，年轻人中的脂质水平确实可以指示未来的CVD风险，因此，建议降低脂质的策略可能对该年龄组有益。

高血压在世界成年人口中普遍存在，并且是心脏病和中风的主要危险因素。高盐饮食（HSD）可以导致高血压，但缺乏有关盐摄入如何影响病理的完整细节。最近的研究表明，粪便从高血压动物向正常血压动物的转移可导致受体中的高血压，这表明肠道菌群发挥了作用。现在，Yan及其同事表明，HSD上的大鼠改变了肠道菌群，特别是脆弱拟杆菌的数量减少了。对HSD喂养的大鼠的肠道代谢产物和物质的分析还表明，由脆弱的B产生的花生四烯酸（AA）的水平-低，调节压力的压力激素皮质酮水平升高。研究小组继续证明，脆弱类B菌培养物的上清液可以防止HSD喂养的小鼠肠道组织中皮质酮的产生，而用AA治疗也是如此。此外，发现高血压人群的粪便中脆弱的B和AA均低于健康人。结果表明，脆弱的B和AA通常会抑制皮质酮的产生，因此可能成为高血压治疗策略的新靶标。