Diabetes affects endothelial cell function and alters fibrin clot formation in a microvascular flow model: A pilot study

• Authors: Lorenz Jenny, University of Bern; Andreas Melmer, University Hospital of Bern; Markus Laimer, University Hospital of Bern; Elaissa Hardy, Emory University; Wilbur Lam, Emory University; Verena Schroeder, University of Bern
• Journal Title: DIABETES & VASCULAR DISEASE RESEARCH
• Volume: Volume 17, Number 1
• Publisher: SAGE PUBLICATIONS LTD | 2020-01-01, Pages 1479164120903044-1479164120903044
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1177/1479164120903044
• Subjects: Health Sciences, Medicine and Surgery; Biology, Cell; Health Sciences, Nutrition
• Keywords: Science & Technology; Life Sciences & Biomedicine; Endocrinology & Metabolism; Peripheral Vascular Disease; Cardiovascular System & Cardiology; Blood coagulation; diabetes mellitus; endothelial cells; microfluidics; MANNOSE-BINDING LECTIN; CARDIOVASCULAR-DISEASE; COMPLEMENT ACTIVATION; PLASMA-LEVELS; TYPE-2; MELLITUS; MECHANISMS; FIBRONECTIN; COAGULATION; PHENOTYPE

Abstract

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.