Understanding the role of vascular stretch on modulation of VWF and ANGPT-2 in continuous flow left ventricular assist device (CF-VAD) patients

Abstract

Non-surgical bleeding is a common complication in patients on continuous flow left ventricular assist device (CF-VAD) support. This study investigates how the transition from cyclic to constant stretch following CF-VAD implantation affects endothelial biosynthesis and release of Von Willebrand factor (VWF) and angiopoietin-2 (ANGPT-2), two molecules that play an essential role in the development of non-surgical bleeding. Human aortic endothelial and umbilical vein endothelial cells (HAECs and HUVECs) were cultured within a uniaxial stretch device that mimics stretch associated with both normal pulsatile and CF-VAD conditions. Following 72 hours of stretch, transcriptional regulation, intracellular accumulation, and secretion of VWF and ANGPT-2 were evaluated using molecular expression profiling and immunofluorescence microscopy. Constant stretch associated with CF-VADs upregulates transcriptional levels of VWF and ANGPT-2 in HAECs and HUVECs compared to physiological cyclic stretch (p < 0.05). Transcriptional increases in both VWF and ANGPT-2 in HAECs also resulted in increased intracellular protein levels of VWF and ANGPT-2 measured using ELISA, western blots and immunofluorescence microscopy, whereas in HUVECs, the intracellular increase was evident only with western blots and immunofluorescence microscopy. Finally, constant stretch appears to promote ANGPT-2 release and inhibit release of VWF from both HAECs and HUVECs compared to cyclic stretch. Our study found that constant stretch upregulates the production of both VWF and ANGPT-2. However, while the release of ANGPT-2 is elevated under constant stretch, the release of VWF declines, resulting in elevated extracellular levels of ANGPT-2, but not VWF.

Graphical abstract: Understanding the role of vascular stretch on modulation of VWF and ANGPT-2 in continuous flow left ventricular assist device (CF-VAD) patients

Supplementary files

Article information

Article type
Paper
Submitted
15 Dec 2024
Accepted
25 Apr 2025
First published
25 Apr 2025
This article is Open Access
Creative Commons BY-NC license

Lab Chip, 2025, Advance Article

Understanding the role of vascular stretch on modulation of VWF and ANGPT-2 in continuous flow left ventricular assist device (CF-VAD) patients

J. P. Sah, J. E. Dominguez De Leon, I. C. Berg, B. L. Cornelius, D. B. Dekle, E. Ismail, X. Cheng, G. A. Giridharan and P. Sethu, Lab Chip, 2025, Advance Article , DOI: 10.1039/D4LC01065E

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