A common observation in patients who develop atherosclerosis is that plaques often occur in specific areas of blood vessels such as the coronary arteries, the carotid arteries, and the iliac arteries. These vessels are often referred to as atheroprone vessels. These vessels are similar in that they all display complex and irregular hemodynamics. It is believed that the blood flow patterns within these vessels are a main culprit for the development of atherosclerotic lesions, causing changes in the tissue such as gene up/down regulation. However, to what extent is the glycocalyx responsible for these occurrences?
The goal of this research is to determine what role the glycocalyx plays in preventing atherosclerosis by examining the effects of varying levels of disturbed flow, such as those observed in atheroprone vessels, on the glycocalyx of endothelial cells. By analyzing the resulting structure of the glycocalyx in response to disturbed flow, we hope to gain a better understanding of exactly how the glycocalyx helps prevent atherosclerosis, if it does so at all. Doing so may allow for the future development of glycocalyx based therapeutics that prevent the development of atherosclerosis.
Harding, I. C., Mitra, R., Mensah, S. A., Nersesyan, A., Bal, N. N., & Ebong, E. E. Endothelial barrier reinforcement relies on flow-regulated glycocalyx, a potential therapeutic target Biorheology. 2019;56(2-3):131-149. LINK
Harding, I. C., Mitra, R., Mensah, S. A., Herman, I. M., & Ebong, E. E. Pro-atherosclerotic disturbed flow disrupts caveolin-1 expression, localization, and function via glycocalyx degradation Journal of Translational Medicine. 2018 Dec 18;16(1):364. LINK
Mitra, R., Qiao, J., Madhavan, S., O'Neil, G. L., Ritchie, B., Kulkarni, P., & Hamilton, J. A. The comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammation Translational Medicine Communications, 2018;3:10. LINK
Zeng, Ye, et al. Fluid shear stress induces the clustering of heparan sulfate via mobility of glypican-1 in lipid rafts American Journal of Physiology-Heart and Circulatory Physiology305.6 (2013): H811-H820. LINK
Ebong, Eno Essien, David C. Spray, and John M. Tarbell. Glycocalyx Core Proteins Selectively Mediate Endothelial NOS activation and Cell Alignment in Response to Shear Stress. The FASEB Journal27.1_MeetingAbstracts (2013): 379-3.
Ebong, Eno E., and Natacha DePaola. Specificity in the participation of connexin proteins in flow-induced endothelial gap junction communication Pflügers Archiv-European Journal of Physiology465.9 (2013): 1293-1302. LINK
Ebong, Eno Essien, David C. Spray, and John M. Tarbell. The Glypican-1 HS Core Protein of the Glycocalyx is Important for Flow-induced Endothelial NOS Activation but not Cell Remodeling. The FASEB Journal25.1_MeetingAbstracts (2011): 39-9.
Ebong, E. E., D. C. Spray, and J. M. Tarbell. The Roles of HS and Its Glypican-1 Core Protein in Flow-Induced Endothelial NOS Activation and Cell Remodeling ASME 2011 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2011. LINK
Ebong, Eno Essien, David C. Spray, and John M. Tarbell. The Endothelial Glycocalyx In Vitro: Its Structure and The Role of Heparan Sulfate and Glypican-1 in eNOS Activation by Flow. The FASEB Journal24.1_MeetingAbstracts (2010): 784-8.
Ebong, E. E., D. C. Spray, and J. M. Tarbell. The role of the endothelial glycocalyx layer in transducing fluid shear stress into intracellular signaling events Biorheology. Vol. 45. No. 1-2. NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS: IOS PRESS, 2008.
Ebong, Eno Essien, Sanghee Kim, and Natacha DePaola. Flow regulates intercellular communication in HAEC by assembling functional Cx40 and Cx37 gap junctional channels American Journal of Physiology-Heart and Circulatory Physiology290.5 (2006): H2015-H2023. LINK