当前位置: X-MOL 学术Circ. Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
In This Issue.
Circulation Research ( IF 20.1 ) Pub Date : 2020-09-10 , DOI: 10.1161/res.0000000000000437
Ruth Williams

Kawasaki disease (KD), which affects young children and has unknown etiology, is characterized by fever, rash and inflammation of the blood vessels that, in some cases, leads to permanent damage of the coronary arteries. Because hyperactivated platelets is a feature of KD and because platelets were recently reported to produce a repair-promoting factor—a microRNA called miR-223—Zhang and colleagues hypothesized that variability in miR-223 production or response may explain why some KD patients fair worse than others. Platelets isolated from KD patients with severe damage (arterial aneurysms) were found to produce significantly lower levels of miR-223 than those from patients who faired better (no aneurysms). And, in a mouse model of KD, lack of miR-223 resulted in more extreme arterial damage than seen in control KD animals. Furthermore, administration of miR-223 or inhibition of platelet derived growth factor (PDGF) could prevent such excessive damage—previous work had shown miR-223 blocks PDGF in vascular smooth muscle cells to prevent these cells from excess proliferation. Together the results indicate that boosting miR-223 or inhibiting PDGF may be therapeutic strategies to minimize the chance of permanent vascular damage in KD patients.


Diabetes increases a person’s risk of developing atherosclerosis and, while the underlying link isn’t entirely clear, it is known that chronic hyperglycemia induces white blood cell production, which promotes monocyte infiltration into plaques. Intriguingly however, treatments that temporarily lower blood sugar do not eliminate CVD risk, and people with impaired glucose tolerance (IGT), characterized by occasional spikes of hyperglycemia, are also prone to CVD. Flynn and colleagues thus considered that intermittent hyperglycemia might also worsen atherogenesis. To find out, the team gave atherosclerosis-prone animals a series of glucose injections over the course of eight hours, one day per week for 10 weeks. Sure enough, plaque burden and production of monocytes and neutrophils (myelopoiesis) was increased in glucose recipients compared with controls. In fact, a single day of injections was enough to boost myelopoiesis. The team went on to show that neutrophil-produced proteins S100A8 and A9, known as alarmins, were responsible for the myelopoiesis and that inhibiting their action prevented the increased plaque burden. The results show that even occasional blood sugar spikes can fuel atherosclerosis and suggest anti-alarmin treatments may prevent the risk in IGT and diabetic patients.


In the mouse embryo, cardiomyocytes are highly proliferative, but soon after birth, the cells become binucleated and undergo no further divisions. With this transition, the regenerative capacity of the heart dwindles. The mechanism underlying this postnatal cytokinesis block is a mystery, but around the same time, the population of cardiac fibroblasts expands changing the composition of the heart’s extracellular matrix (ECM), suggesting these cells, or the ECM, might be involved. To find out, Wu and colleagues cultured postnatal rat primary cardiomyocytes with either postnatal fibroblasts, postnatal ECM or embryonic ECM. While both the postnatal fibroblasts and ECM were found to prevent cytokinesis, embryonic ECM permitted a greater proportion of the cardiomyocytes to divide. Comparing the proteomes of postnatal and embryonic ECMs, the team identified candidate cytokinesis-promoting factors in the embryonic ECM, tested the factor’s division-driving capacity on cardiomyocytes in vitro and found two—SLIT2 and nephronectin—had such ability. Both factors could also promote heart cell cytokinesis when injected into postnatal mice. These two factors may be novel targets for promoting adult cardiomyocyte proliferation and regeneration after heart injury, suggest the authors.



中文翻译:

在这个问题上。

川崎病(KD)影响幼儿,病因不明,其特征是发烧,皮疹和血管发炎,在某些情况下会导致冠状动脉的永久性损伤。由于活化过高的血小板是KD的特征,并且由于最近有报道称血小板会产生修复促进因子(一种称为miR-223的microRNA),Zhang及其同事推测,miR-223产生或反应的变异性可以解释为什么某些KD患者病情更差相对于其它的。发现从患有严重损伤(动脉瘤)的KD患者中分离出的血小板产生的miR-223的水平明显低于那些表现较好(无动脉瘤)的患者。而且,在KD小鼠模型中,与对照KD动物相比,缺乏miR-223导致了更大的动脉损伤。此外,施用miR-223或抑制血小板衍生生长因子(PDGF)可以预防此类过度损伤-先前的研究表明,miR-223可以阻断血管平滑肌细胞中的PDGF,以防止这些细胞过度增殖。在一起的结果表明,增强miR-223或抑制PDGF可能是使KD患者永久性血管损伤机会最小化的治疗策略。


糖尿病会增加人患动脉粥样硬化的风险,虽然其内在联系尚不完全清楚,但众所周知,慢性高血糖症会诱发白细胞产生,从而促进单核细胞浸入斑块。有趣的是,暂时降低血糖的治疗方法并不能消除CVD的风险,而且以偶尔出现高血糖发作为特征的葡萄糖耐量降低(IGT)的人也容易发生CVD。因此,Flynn及其同事认为,间歇性高血糖也可能会使动脉粥样硬化恶化。为了找到答案,研究小组在八个小时的过程中,向易患动脉粥样硬化的动物进行了一系列葡萄糖注射,每周一次,持续10周。果然,与对照组相比,葡萄糖受体的空斑负担和单核细胞和中性粒细胞(骨髓生成)的产生增加。实际上,一天注射就足以促进骨髓生成。研究小组继续表明,嗜中性粒细胞产生的蛋白质S100A8和A9(称为警报蛋白)与骨髓生成有关,抑制它们的作用可防止斑块负担增加。结果表明,即使偶尔出现血糖升高也可加剧动脉粥样硬化,并表明抗阿拉明素治疗可预防IGT和糖尿病患者的风险。


在小鼠胚胎中,心肌细胞高度增殖,但出生后不久,细胞变为双核,并且不再进一步分裂。随着这种转变,心脏的再生能力下降。这种产后胞质分裂阻滞的潜在机制是一个谜,但是大约在同一时间,心脏成纤维细胞的数量不断扩大,改变了心脏的细胞外基质(ECM)的成分,表明这些细胞或ECM可能参与其中。为了找出答案,Wu及其同事用产后成纤维细胞,产后ECM或胚胎ECM培养了产后大鼠原代心肌细胞。虽然发现产后成纤维细胞和ECM均能防止胞质分裂,但胚胎ECM允许更多比例的心肌细胞分裂。比较产后和胚胎ECM的蛋白质组,该团队在胚胎ECM中鉴定了候选的胞质分裂促进因子,并在体外测试了该因子在心肌细胞上的分裂驱动能力,并发现具有这种能力的两个细胞(SLIT2和肾素)。当注射到产后小鼠中时,这两种因素也可能促进心脏细胞的胞质分裂。这组作者认为,这两个因素可能是促进成人心肌损伤后心肌细胞增殖和再生的新靶标。

更新日期:2020-09-11
down
wechat
bug