Date of Graduation
Bachelor of Science in Biomedical Engineering
Hypertension is a disorder prevalent in adults around the world and is a common attributable cause of heart disease and mortality . Calcification is much more common in the aortic valve than the other three heart valves . Aortic valve interstitial cells (VICs), the principal cell type found in the human aortic valve, have been linked to disease development when they change in phenotype to become osteoblast like cells . The phenotypes of these cells play a role in the development of calcification in the aortic valves .
Angiotensin II is a hormone in the body that has been implicated to stimulate inflammation in heart valves and is linked to the development of heart valve disease . Losartan (AT1R antagonist) and PD123319 (AT2R antagonist) are commercially available drugs to prevent ang-II from binding to ang-II receptors on the cells . There are certain protein signatures (RUNX2, αSMA, Ki-67, TGFβ1, Vimentin, and Calponin) that can be observed to determine if VICs are being activated in the presence of ang-I or ang-II with and without the presence of receptor antagonists.
Cells were cultured in 10% media with six treatment groups and one control: angiotensin I (ang-I) without an inhibitor, angiotensin II (ang-II) without an inhibitor, angiotensin I + Losartan (ang-I + Los), angiotensin II + Losartan (ang -I + Los), angiotensin I + PD123319 (ang-I + PD), and angiotensin II + PD123319 (ang-II + PD). Expression of protein signatures was assessed using immunocytochemistry. Results displayed phenotypic change in the form of increased expression of protein signatures in VICs with treatment groups. Most VICs were inhibited in the presence of losartan, demonstrating that the binding of ang II to AT1R is causing increased activation of the VICs.
Scalise, Sophia, "Role of Local Renin-Angiotensin System in Altering Valve Interstitial Cell Phenotype" (2018). Biomedical Engineering Undergraduate Honors Theses. 51.
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