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Biological factors in plasma from diabetes mellitus patients enhance hyperglycaemia and pulsatile shear stress-induced endothelial cell apoptosis
Liu X.F.1; Yu J.Q.1; Dalan R.4; Liu A.Q.1; Luo K.Q.1
2014
Source PublicationIntegrative Biology (United Kingdom)
ISSN17579708 17579694
Volume6Issue:5Pages:511-522
Abstract

People suffering from Diabetes Mellitus (DM) are prone to an array of vascular complications leading to end organ damage. The hallmark of these vascular complications is endothelium dysfunction, which is caused by endothelial cell (EC) apoptosis. Although the endothelial cell (EC) dysfunction induced by hyperglycaemia and fluid shear stress has been studied, the effects of biological factors in the blood of DM patients on EC integrity have not been reported in the in vitro models that mimic the physiological pulsatile nature of the vascular system. This study reports the development of a hemodynamic lab-on-a-chip system to investigate this issue. The pulsatile flow was applied to a monolayer of endothelial cells expressing a fluorescence resonance energy transfer (FRET)-based biosensor that changes colour from green to blue in response to caspase-3 activation during apoptosis. Plasma samples from healthy volunteers and DM patients were compared to identify biological factors that are critical to endothelial disruption. Three types of microchannels were designed to simulate the blood vessels under healthy and partially blocked pathological conditions. The results showed that EC apoptosis rates increased with increasing glucose concentration and levels of shear stress. The rates of apoptosis further increased by a factor of 1.4-2.3 for hyperglycaemic plasma under all dynamic conditions. Under static conditions, little difference was detected in the rate of EC apoptosis between experiments using plasma from DM patients and glucose medium, suggesting that the effects of hyperglycaemia and biological factors on the induction of EC apoptosis are all shear flow-dependent. A proteomics study was then conducted to identify biological factors, demonstrating that the levels of eight proteins, including haptoglobin and clusterin, were significantly down-regulated, while six proteins, including apolipoprotein C-III, were significantly up-regulated in the plasma of DM patients compared to healthy volunteers. This hemodynamic lab-on-a-chip system can serve as a high throughput platform to assess the risk of vascular complications of DM patients and to determine the effects of therapeutics or other interventions on EC apoptosis. © 2014 The Royal Society of Chemistry.

DOI10.1039/c3ib40265g
URLView the original
Indexed BySCIE
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000339930500009
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Document TypeJournal article
CollectionFaculty of Health Sciences
Affiliation1.Nanyang Technological University
2.Yong Loo Lin School of Medicine
3.Duke-NUS Medical School Singapore
4.Tan Tock Seng Hospital
Recommended Citation
GB/T 7714
Liu X.F.,Yu J.Q.,Dalan R.,et al. Biological factors in plasma from diabetes mellitus patients enhance hyperglycaemia and pulsatile shear stress-induced endothelial cell apoptosis[J]. Integrative Biology (United Kingdom),2014,6(5):511-522.
APA Liu X.F.,Yu J.Q.,Dalan R.,Liu A.Q.,&Luo K.Q..(2014).Biological factors in plasma from diabetes mellitus patients enhance hyperglycaemia and pulsatile shear stress-induced endothelial cell apoptosis.Integrative Biology (United Kingdom),6(5),511-522.
MLA Liu X.F.,et al."Biological factors in plasma from diabetes mellitus patients enhance hyperglycaemia and pulsatile shear stress-induced endothelial cell apoptosis".Integrative Biology (United Kingdom) 6.5(2014):511-522.
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