Despite advancements in the prevention and treatment of atherosclerotic cardiovascular disease, it remains the leading cause of death, disability, and health costs in the US and worldwide. During atherosclerosis, there is increased inflammation and the development of endothelial dysfunction. Concurrent with these processes, the endothelial glycocalyx, a layer of glycoproteins and polysaccharides that interfaces with blood flow, is degraded. The glycocalyx is a major structure maintaining vascular barrier function, reducing thrombosis during vascular injury and serves as an anti-inflammatory factor that reduces the extravasation of circulating immune cells. In this proposal, we aim to create glycocalyx-mimetic therapeutics that circulate in the blood and accumulate on the surface of the endothelial cells to restore barrier function during atherosclerosis and vascular injury. To this end, we will explore the use of marine polysaccharides that have a structure similar to molecules in the glycocalyx and can be given as oral therapy for atherosclerosis. Our preliminary and published studies have shown that the marine polysaccharide rhamnan sulfate can accumulate on the surface of endothelial cells and reduces inflammation and lipid uptake in endothelial cells. In addition, we found that rhamnan sulfate prevented arteriothrombosis during vascular injury. We will evaluate rhamnan sulfate as a potential therapy for reducing the formation of atherosclerotic plaques and reducing vascular inflammation. To achieve this goal, we will carry out the following specific aims: (1) examine the effectiveness of marine polysaccharides in reducing inflammation and lipid uptake in vascular cells; and (2) examine the utility of rhamnan sulfate in reducing atherosclerosis following vascular injury in mice. Together these studies will provide an evaluation of the therapeutic potential of rhamnan sulfate for vascular disease and injury. As rhamnan sulfate is relatively inexpensive and has been consumed by millions of people as part of their diet, it would present an easily implementable adjuvant therapy to lipid lowering drugs and other treatments for atherosclerotic disease.

Public Health Relevance

Despite advancements in the prevention and treatment of atherosclerotic cardiovascular disease, it remains the leading cause of death, disability, and health costs in the US and worldwide. This is a proposal to develop a novel therapy for atherosclerosis and vascular injury based on the marine polysaccharide rhamnan sulfate that is affordable, safe and can be used in combination with current treatments.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EB024147-01A1
Application #
9387566
Study Section
Atherosclerosis and Inflammation of the Cardiovascular System Study Section (AICS)
Program Officer
Rampulla, David
Project Start
2017-09-15
Project End
2019-08-31
Budget Start
2017-09-15
Budget End
2018-08-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78759
Patil, Nikita P; Le, Victoria; Sligar, Andrew D et al. (2018) Algal Polysaccharides as Therapeutic Agents for Atherosclerosis. Front Cardiovasc Med 5:153
Veith, Austin P; Henderson, Kayla; Spencer, Adrianne et al. (2018) Therapeutic strategies for enhancing angiogenesis in wound healing. Adv Drug Deliv Rev :