Graduation Year
2019
Date of Submission
12-2018
Document Type
Campus Only Senior Thesis
Degree Name
Bachelor of Arts
Department
W.M. Keck Science Department
Second Department
Biology
Reader 1
Sanjeev Datar, UCSF
Reader 2
John Milton
Terms of Use & License Information
OCLC Record Number
1090356326
Abstract
An important cause of pulmonary arterial hypertension (PAH) in children with congenital heart disease (CHD) is increased pulmonary blood flow (PBF). To gain a better understanding of the disease process, the changes in biochemical pathways and metabolism of pulmonary arterial smooth muscle cells (PASMCs) were studied using a unique surgical ovine model of increased pulmonary blood flow. PASMCs isolated from 4-week-old lambs with increased PBF (shunt) showed lower oxygen consumption rates and lower extracellular acidification rates linked to glutamine metabolism when compared to controls. Shunt and control PASMCs both exhibited a switch into the reverse tricarboxylic acid (TCA) cycle, while only shunt cells showed a decrease of glucose being transformed into Acetyl CoA to enter the forward TCA cycle. Shunt PASMCs also demonstrated increased levels of yes-associated protein 1 (YAP1) expression in the nucleus. These results indicate changes in glutamine metabolism, glucose metabolism, and protein signaling cascades associated with increased mechanical forces in the setting of increased PBF, as seen in PAH in children with CHD.
Recommended Citation
Seifert, Elena, "Metabolic Changes in Pulmonary Arterial Smooth Muscle Cells Exposed to Increased Mechanical Forces from an Ovine Model of Congenital Heart Disease with Increased Pulmonary Blood Flow" (2019). CMC Senior Theses. 2094.
https://scholarship.claremont.edu/cmc_theses/2094
This thesis is restricted to the Claremont Colleges current faculty, students, and staff.
