Restoration of Mechanotransduction in Blood Vessels Using Microsphere

Presenter: Yusra Habib

Faculty Sponsor: Xiaohui Frank Zhang

School: UMass Amherst

Research Area: Medical Sciences

Session: Poster Session 6, 4:15 PM - 5:00 PM, 163, C17

ABSTRACT

Cells covering the inner walls of the blood vessels, known as endothelial cells (ECs), are constantly exposed to mechanical stimulation from the blood and turning this to biochemical product is Mechanotrnasduction. Specifically, the endothelial glycocalyx, a gel-like layer exterior consisting of core proteins and glycosinoglycans (GAGs), continuously senses this flow which contributes to vascular homeostasis by controlling nitric oxide (NO) production, a potent vasodilator. The study confirms that glycocalyx degradation due to pathological conditions leads to the loss of mechanotransduction, which leads to loss of NO bioavailability and, hence, vascular dysfunction. Here, we study the effects of glycocalyx degradation on NO production through mouse brain endothelial cells (bEnd.3) and evaluate the microsphere-driven therapeutic approaches to restore glycocalyx integrity.


The study uses an in vitro model stimulating healthy and pathological conditions, including degradation of enzymatic cleavage of glycocalyx (Heparinase I & III) and inflammatory cytokine(TNF-α). NO production is assessed using a fluorescent marker under four experimental conditions: intact glycocalyx, degraded glycocalyx, inflammation-induced damage glycocalyx, and microsphere-treated glycocalyx. The microspheres have been developed to mimic GAGs; therefore, when they get attached to core proteins commonly found on ECs like syndecan-4 and glypican-1, the glycocalyx can sense more of the flow, which would increase NO production.


The results of this research should provide a mechanistic understanding of the link between glycocalyx degradation and NO production, filling an important gap in vascular biology. Furthermore, it assesses the capability of biomaterials-based approaches to restore endothelial glycocalyx and thus opens up a new avenue for therapeutics in vascular diseases such as diabetes, atherosclerosis, and hypertension.