Experimental Haemostasis Group, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.
University Clinic for Diabetology, Endocrinology, Nutritional Medicine and Metabolism, University Hospital of Bern, Inselspital, Bern, Switzerland.
Diab Vasc Dis Res. 2020 Jan-Feb;17(1):1479164120903044. doi: 10.1177/1479164120903044.
Diabetes is a proinflammatory and prothrombotic condition that increases the risk of vascular complications. The aim of this study was to develop a diabetic microvascular flow model that allows to study the complex interactions between endothelial cells, blood cells and plasma proteins and their effects on clot formation. Primary human cardiac microvascular endothelial cells from donors without diabetes or donors with diabetes (type 1 or type 2) were grown in a microfluidic chip, perfused with non-diabetic or diabetic whole blood, and clot formation was assessed by measuring fibrin deposition in real time by confocal microscopy. Clot formation in non-diabetic whole blood was significantly increased in the presence of endothelial cells from donors with type 2 diabetes compared with cells from donors without diabetes. There was no significant difference in clot formation between non-diabetic and diabetic whole blood. We present for the first time a diabetic microvascular flow model as a new tool to study clot formation as a result of the complex interactions between endothelial cells, blood cells and plasma proteins in a diabetes setting. We show that endothelial cells affect clot formation in whole blood, attributing an important role to the endothelium in the development of atherothrombotic complications.
糖尿病是一种促炎和促血栓形成的疾病,会增加血管并发症的风险。本研究旨在开发一种糖尿病微血管血流模型,以研究内皮细胞、血细胞和血浆蛋白之间的复杂相互作用及其对血栓形成的影响。从无糖尿病或糖尿病(1 型或 2 型)供体中培养的原代人心脏微血管内皮细胞在微流控芯片中生长,用非糖尿病或糖尿病全血灌注,并通过共聚焦显微镜实时测量纤维蛋白沉积来评估血栓形成。与无糖尿病供体的细胞相比,来自 2 型糖尿病供体的内皮细胞存在时,非糖尿病全血中的血栓形成明显增加。非糖尿病和糖尿病全血之间的血栓形成没有显著差异。我们首次提出了一种糖尿病微血管血流模型,作为一种新工具,用于研究在糖尿病环境下内皮细胞、血细胞和血浆蛋白之间的复杂相互作用导致的血栓形成。我们表明,内皮细胞会影响全血中的血栓形成,这表明内皮细胞在动脉血栓并发症的发展中起着重要作用。