Date of Graduation

5-2022

Document Type

Thesis

Degree Name

Bachelor of Science in Biomedical Engineering

Degree Level

Undergraduate

Department

Biomedical Engineering

Advisor/Mentor

Balachandran, Kartik

Abstract

Cardiovascular diseases affect the older population with limited treatments available. Aortic valve stenosis is a cardiovascular disease in which the aortic valve narrows, causing blood flow constriction and calcification.¹ The only treatment is to replace the valve, which can be costly and lead to other health complications.

The renin-angiotensin system (RAS) is a pathway that helps with maintaining cardiovascular homeostasis. Angiotensin I (ANGI) and II (ANGII) are hormones in the RAS that cause an increase in inflammation, stress, and blood pressure by binding to the Angiotensin Type 1 Receptor (AT1R).¹ Gelatin-based valve thin film (vTF) platforms were fabricated to investigate whether the contractility response to heart valve interstitial cells (VICs) can be regulated using RAS mediators and inhibitors.¹ The RAS mediators are ANGI and ANGII and the RAS inhibitors are AT1R and angiotensin-converting enzyme (ACE) inhibitors.

Results indicate that the contractility stress response of VICs increases due to the increased concentration of ANGI and ANGII in the system. Conversely, the contractile stress response of VICs decreased when ACE or AT1R inhibitors were added. There was approximately 66% more contractile response in VICs activated with ANGII in comparison to VICs with inhibitors.¹ These results were also studied computationally using a MATLAB program called Netflux. Analysis using Netflux supported that there was approximately 66% more contractility stress response in VICs activated using mediators in comparison to inhibitors. These results help further understand the relationship that mediators and inhibitors have with RAS, and thus how they affect the mechanics of the heart.

Utilizing Netflux in future research projects can be used to further understand relationships between mediators or inhibitors in any biological pathways. Additionally, the vTF platform has proved to be a great scaffold for analyzing a biological pathway such as RAS. vTF platforms can be used for future drug screening and development to treat cardiovascular diseases.¹

Keywords

cardiology; cardiovascular disease; engineering; valve thin film; computational biology

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