Fiorelli Susanna, Cosentino Nicola, Porro Benedetta, Fabbiocchi Franco, Niccoli Giampaolo, Fracassi Francesco, Capra Nicolò, Barbieri Simone, Crea Filippo, Marenzi Giancarlo, Cavalca Viviana, Tremoli Elena, Eligini Sonia
Centro Cardiologico Monzino I.R.C.C.S., 20138 Milan, Italy.
Dipartimento di Scienze Cardiovascolari e Toraciche, Fondazione Policlinico Gemelli I.R.C.C.S., Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Biomedicines. 2021 Feb 8;9(2):168. doi: 10.3390/biomedicines9020168.
Netrin-1 is a laminin-like protein that plays a pivotal role in cell migration and, according to the site of its release, exerts both pro and anti-atherosclerotic functions. Macrophages, key cells in atherosclerosis, are heterogeneous in morphology and function and different subpopulations may support plaque progression, stabilization, and/or regression. Netrin-1 was evaluated in plasma and, together with its receptor UNC5b, in both spindle and round monocyte-derived macrophages (MDMs) morphotypes from coronary artery disease (CAD) patients and control subjects. In CAD patients, plaque features were detected in vivo by optical coherence tomography. CAD patients had lower plasma Netrin-1 levels and a higher MDMs expression of both protein and its receptor compared to controls. Specifically, a progressive increase in Netrin-1 and UNC5b was evidenced going from controls to stable angina (SA) and acute myocardial infarction (AMI) patients. Of note, spindle MDMs of AMI showed a marked increase of both Netrin-1 and its receptor compared to spindle MDMs of controls. UNC5b expression is always higher in spindle compared to round MDMs, regardless of the subgroup. Finally, CAD patients with higher intracellular Netrin-1 levels showed greater intraplaque macrophage accumulation in vivo. Our findings support the role of Netrin-1 and UNC5b in the atherosclerotic process.
Netrin-1是一种层粘连蛋白样蛋白，在细胞迁移中起关键作用，并根据其释放部位发挥促动脉粥样硬化和抗动脉粥样硬化功能。巨噬细胞是动脉粥样硬化中的关键细胞，在形态和功能上具有异质性，不同亚群可能支持斑块进展、稳定和/或消退。对冠状动脉疾病（CAD）患者和对照受试者的血浆以及纺锤形和圆形单核细胞衍生巨噬细胞（MDM）形态型中的Netrin-1及其受体UNC5b进行了评估。在CAD患者中，通过光学相干断层扫描在体内检测斑块特征。与对照组相比，CAD患者的血浆Netrin-1水平较低，MDM中该蛋白及其受体的表达较高。具体而言，从对照组到稳定型心绞痛（SA）和急性心肌梗死（AMI）患者，Netrin-1和UNC5b呈逐渐增加趋势。值得注意的是，与对照组的纺锤形MDM相比，AMI的纺锤形MDM中Netrin-1及其受体均显著增加。无论亚组如何，纺锤形MDM中UNC5b的表达始终高于圆形MDM。最后，细胞内Netrin-1水平较高的CAD患者在体内显示出更大的斑块内巨噬细胞积聚。我们的研究结果支持Netrin-1和UNC5b在动脉粥样硬化过程中的作用。
