Disturbed Flow image

Modeling vascular flow dynamics in cell culture and animal models

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?

Cancer Attachment image

Role of mechanobiology and glycocalyx mechanotransducer in atherosclerosis and cancer

Cancer cells have been known to attach to endothelial cells during metastasis. The glycocalyx on endothelial cells plays a significant role in the attachment of cancer cells to the endothelium.  The degradation of endothelial glycocalyx (GCX), which can be caused by the presence of cytokines released by metastatic tumors, facilitates the formation of ligand-receptor complexes on the surfaces of both cancer and endothelial cells, causing increased levels of cancer cell attachment. Currently, we have shown that the glycosaminoglycan sialic acid plays a significant role in the attachment of cancer cells to the endothelium.

Endothelial cell image

Endothelial cell and glycocalyx targeted nanoparticle drug delivery

The dysfunction of the glycocalyx in athero-prone regions in conjunction with the rising popularity of nano-scale therapeutics points to a possibility of a nanoparticle based glycocalyx treatment. The glycocalyx has a pore size cutoff of 7nm under healthy conditions, which become larger when its integrity is compromised. Also when the glycocalyx is shed there may be more receptors exposed to the bloodflow. By utilizing circulating nanoparticles we aim to target particles to specific regions undergoing atherogenesis to prevent further damage.  So far we have shown that the glycocalyx plays a role in 10nm sized polymer coated nanosphere uptake, visualized by fluorescently tagging components of the layer and particles. 

Glycocalyx Sialic Acid

Endothelial cell glycocalyx structure, function, and role in endothelial mechanobiology

In current research, the glycocalyx is most often analyzed using fluorescent microscopy techniques with spatial resolution in the range of several hundred nanometers. While this resolution is adequate to quantify the presence or thickness of the glycocalyx, it does not allow for more detailed, qualitative analysis of the structure of individual glycocalyx components.

Glycocalyx Word Art

Glycocalyx and Inflammation

Over the past several decades, it has been shown that the development of atherosclerosis, which had widely been associated as a consequence of high lipid levels, is, at least in some part, an inflammatory process. These discoveries have led to investigations on the effects of inflammation on the glycocalyx and found that inflammation may lead to degradation of the endothelial glycocalyx. The Ebong lab would like to further investigate inflammation and its effect on the glycocalyx by using high resolution imaging to determine the detailed structure of the glycocalyx pre- and post-inflammation.

Endothelial barrier reinforcement relies on flow-regulated glycocalyx, a potential therapeutic target

Harding, I. C., Mitra, R., Mensah, S. A., Nersesyan, A., Bal, N. N., & Ebong, E. E. (2019). Endothelial barrier reinforcement relies on flow-regulated glycocalyx, a potential therapeutic target Biorheology, (Preprint), 1-19.

Pro-atherosclerotic disturbed flow disrupts caveolin-1 expression, localization, and function via glycocalyx degradation

Harding, I. C., Mitra, R., Mensah, S. A., Herman, I. M., & Ebong, E. E. (2018). Pro-atherosclerotic disturbed flow disrupts caveolin-1 expression, localization, and function via glycocalyx degradation Journal of translational medicine, 16(1), 364.

Ultrasmall gold nanorods: synthesis and glycocalyx-related permeability in human endothelial cells

Cheng, M. J., Bal, N. N., Prabakaran, P., Kumar, R., Webster, T. J., Sridhar, S., & Ebong, E. E. (2019). Ultrasmall gold nanorods: synthesis and glycocalyx-related permeability in human endothelial cells International journal of nanomedicine, 14, 319.International journal of nanomedicine14 (2019): 319.

The comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammation

Mitra, R., Qiao, J., Madhavan, S., O’Neil, G. L., Ritchie, B., Kulkarni, P., & Hamilton, J. A. (2018). The comparative effects of high fat diet or disturbed blood flow on glycocalyx integrity and vascular inflammation Translational Medicine Communications, 3(1), 10.

Selenium Nanoparticles: Proposed Endothelial Glycocalyx-Targeted Atherosclerosis Treatment

Mitra R., P.P., Ming J. Cheng, Eno E. Ebong, Selenium Nanoparticles: Proposed Endothelial Glycocalyx-Targeted Atherosclerosis Treatment Biomaterials Forum, 2017. 39(3): p. 15-16, 18.