In peripheral artery disease (PAD), blood flow to the limbs is limited as a result of vessel narrowing from atherosclerotic plaque build up. The symptoms are particularly noticeable in the legs making walking painful and, as the disease progresses, increasingly limited. Interventions that improve blood flow may alleviate the pain and increase mobility. To that end, McDermott and colleagues investigated the possible benefits of drinking cocoa, on the basis that natural flavanols in chocolate are thought to help blood vessel function. A small study of PAD patients previously showed that consuming 40 g of dark chocolate could increase subjects’ walking distances (in timed treadmill tests). Now, McDermott and colleagues have studied patients over a 6-month period in which subjects drank either cocoa or a placebo three times daily. At the end of the study, patients who drank cocoa walked significantly farther in timed tests than those on the placebo. Analyses of the patients’ muscles also revealed that the cocoa drinkers had increased blood perfusion, as well as increased capillary density and mitochondrial activity. Though the results of this small-scale, pilot study are encouraging, they now require validation in larger controlled trials, say the authors.

Sleep-disordered breathing (SDB) is an umbrella term for any chronic condition involving the complete or partial interruption of breathing (apnea) during sleep. Aside from daytime sleepiness, individuals with SDB run the risk of developing arrhythmias, such as atrial fibrillation, which are more prevalent in SDB sufferers. At the cellular level, arrhythmias are associated with increased activity of the enzyme Ca/calmodulin-dependent protein kinase II (CaMKII), which regulates cellular electrophysiology. But levels of CamKII activity have not been investigated in SDB patients. Lebek and colleagues now show, in a study of 113 patients undergoing heart surgery, that those with SDB (approximately half of the subjects) had higher CamKII in biopsied myocardium samples than those without the condition. Furthermore, this CamKII increase was associated with other proarrhythmic alterations to the tissue including, increased reactive oxygen species production, enhanced phosphorylation of a major sodium channel, and consequent late firing of sodium currents. Importantly, these alterations could be prevented by pharmacological inhibition of CamKII, suggesting that such an inhibitor could be a novel treatment strategy for SDB patients to reduce their arrhythmia risk.

Growth and remodeling of blood vessels are essential processes during development and wound healing but can also be pathological in certain disorders. For example, neointimal overgrowth can lead to vessel narrowing (stenosis) in atherosclerosis, while angiogenesis in tumors can trigger expansion and metastasis. Although the vascular system exists in three dimensions, typical studies and measurements of remodeling and growth involve two-dimensional imaging techniques. Becher and colleagues have now employed a recently developed imaging approach called Adipo-Clear, which involves whole-tissue clearing and immunolabelling, to view vessels in 3D. Combining the technique with cutting-edge light-sheet fluorescence microscopy, the team examined the brachial cephalic and carotid arteries of mice at different time points after ligation-induced injury, showing growth of the neointima and of new vessels in the perivascular region. They also examined atherosclerotic plaques—their volume, geometry, and topology—in mice, and a radial artery of a man with coronary artery disease. These proof-of-principal experiments now set the stage for the use of Adipo-Clear and light-sheet fluorescence for studying a wide range of animal models of vascular disease, as well as human specimens.

在外周动脉疾病（PAD）中，由于动脉粥样硬化斑块形成而使血管变窄，导致四肢的血流受到限制。该症状在腿部特别明显，使步行感到痛苦，并且随着疾病的发展，其症状越来越受到限制。改善血液流动的干预措施可以减轻疼痛并增加活动能力。为此，McDermott及其同事研究了饮用可可的好处，其依据是巧克力中的天然黄烷醇被认为有助于血管功能。先前对PAD患者进行的一项小型研究表明，食用40克黑巧克力可以增加受试者的步行距离（在定时跑步机测试中）。现在，McDermott及其同事对患者进行了为期6个月的研究，其中受试者每天喝3次可可或安慰剂。在研究结束时，在定时测试中，喝可可的患者走的距离比安慰剂走的要远得多。对患者肌肉的分析还显示，可可饮用者的血液灌注增加，毛细血管密度和线粒体活性增加。这组作者说，尽管这项小规模的先导研究的结果令人鼓舞，但它们现在需要在较大的对照试验中进行验证。

睡眠呼吸障碍（SDB）是任何慢性疾病的总称，涉及睡眠期间呼吸的全部或部分中断（呼吸暂停）。除了白天嗜睡之外，患有SDB的人还存在发生心律不齐的风险，例如心房纤颤，这在SDB病人中更为普遍。在细胞水平上，心律不齐与Ca /钙调蛋白依赖性蛋白激酶II（CaMKII）的活性增加有关，后者调节细胞的电生理。但是尚未在SDB患者中研究CamKII活性水平。Lebek及其同事现在在一项对113名接受心脏手术的患者的研究中显示，活检心肌样本中患有SDB的患者（约占受试者的一半）的CamKII高于未患病的患者。此外，CamKII的增加与组织的其他心律失常改变有关，包括增加的活性氧产生，增强的主要钠通道的磷酸化以及随后的钠电流放电。重要的是，可以通过药理学上抑制CamKII来防止这些改变，这表明这种抑制剂可能是SDB患者降低心律失常风险的一种新颖治疗策略。

血管的生长和重塑是发育和伤口愈合过程中必不可少的过程，但在某些疾病中也可能是病理性的。例如，新内膜过度生长可导致动脉粥样硬化中的血管变窄（狭窄），而肿瘤中的血管生成可触发扩张和转移。尽管血管系统存在于三个维度，但是对重塑和生长的典型研究和测量涉及二维成像技术。Becher及其同事现在已采用一种最新开发的成像方法Adipo-Clear，该方法涉及整个组织的清除和免疫标记，以3D方式查看血管。研究小组将这项技术与尖端的光片荧光显微镜技术相结合，在结扎诱导的损伤后不同时间点检查了小鼠的臂状头颈和颈动脉，显示新内膜和血管周围区域新血管的生长。他们还检查了小鼠和患有冠状动脉疾病的人的radial动脉中的动脉粥样硬化斑块（其体积，几何形状和拓扑结构）。现在，这些原理证明实验为使用Adipo-Clear和光片荧光技术研究各种血管疾病动物模型以及人类标本奠定了基础。