Heart valve interstitial cells (VICs) undergo activation and proliferation in repair and disease, but the mechanisms are not fully understood. We hypothesize that the establishment of N-cadherin/β-catenin cell-cell contacts may decrease VIC activation, and that Wnt3a/β-catenin signaling may increase VIC proliferation. VIC cultures of different densities are stained for α-SMA, cofilin, TGF-β, pSmad2/3, N-cadherin and β-catenin, and probed for phospho-β-catenin by Western blot. Low density VIC cultures are treated with exogenous Wnt3a and measured for cell number, proliferation, apoptosis, α-SMA, β-catenin, and β-catenin-mediated transcription. β-Catenin siRNA knockdown is used to assess β-catenin specificity. Increased staining of α-SMA, cofilin, TGF-β, pSmad2/3, nuclear β-catenin, and increased phospho-β-catenin are associated with few cell-cell contacts. Wnt3a increased VIC cell number, proliferation, nuclear β-catenin and β-catenin-mediated transcription without affecting activation and apoptosis, and proliferation is abolished by β-catenin siRNA. Thus, N-cadherin/β-catenin cell-cell contacts may inhibit VIC activation and Wnt3a/β-catenin signaling may increase VIC proliferation.

Heart valve interstitial cells (VICs) undergo activation and proliferation in repair and disease, but the mechanisms are not fully understood. We hypothesize that the establishment of N-cadherin/β-catenin cell-cell contacts may decrease VIC activation, and that Wnt3a/β-catenin signaling may increase VIC proliferation. VIC cultures of different densities are stained for α-SMA, cofilin, TGF-β, pSmad2/3, N-cadherin and β-catenin, and probed for phospho-β-catenin by Western blot. Low density VIC cultures are treated with exogenous Wnt3a and measured for cell number, proliferation, apoptosis, α-SMA, β-catenin, and β-catenin-mediated transcription. β-Catenin siRNA knockdown is used to assess β-catenin specificity. Increased staining of α-SMA, cofilin, TGF-β, pSmad2/3, nuclear β-catenin, and increased phospho-β-catenin are associated with few cell-cell contacts. Wnt3a increased VIC cell number, proliferation, nuclear β-catenin and β-catenin-mediated transcription without affecting activation and apoptosis, and proliferation is abolished by β-catenin siRNA. Thus, N-cadherin/β-catenin cell-cell contacts may inhibit VIC activation and Wnt3a/β-catenin signaling may increase VIC proliferation.

Thesis (M.S.)--Chemical Engineering, Georgia Institute of Technology, 2003. / Sambanis Athanassios, Committee Member ; Sotiropoulos Fotis, Committee Member ; Yoganathan Ajit, Committee Chair. Includes bibliographical references (leaves 239-243).

Thesis (M.S.)--Chemical Engineering, Georgia Institute of Technology, 2004. / Sambanis Athanassios, Committee Member ; Sotiropoulos Fotis, Committee Member ; Yoganathan Ajit, Committee Chair. Includes bibliographical references (leaves 239-243).

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 104-125).

No description available.

No description available.

The thesis presents a fluid-structure interaction studies on the hemodynamics of blood flow in the left ventricle and through the mitral valve. The virtual model consists of a mathematical model of the left ventricle coupled with a complex and structurally flexible bi-leaflet valve representing the mitral opening. The mitral valve is a bicuspid valve with anterior and posterior leaflets and it regulates unidirectional blood flow from the left atrium to the left ventricle in the diastole phase. The leaflets are made of chordae, annulus and papillary muscles. The goal of this study is to provide biomedical engineers and clinical physicians with a virtual laboratory tool to understand the dynamics of blood flow in a diseased heart and aid in the design of novel artificial heart valves. To this end, the simulation studies present an increasingly complex model of the heart to evaluate the vortex ring formation and evolution of the diastole phase in the left ventricle; and to characterize the septal-anterior motion in a diseased heart with obstructive hypertrophic cardiomyopathy. Finally, in collaboration with an industrial partner, the fluid-structure modeling framework was used to evaluate the performance of a new accelerated artificial valve tester. / Graduate

Thesis (M.S.)--Rochester Institute of Technology, 2009. / Typescript. Includes bibliographical references (leaves 67-69).

Heart valve disease occurs in adults as well as in pediatric population due to age-related changes, rheumatic fever, infection or congenital condition. Current treatment options are limited to mechanical heart valve (MHV) or bio-prosthetic heart valve (BHV) replacements. Lifelong anti-coagulant medication in case of MHV and calcification, durability in case of BHV are major setbacks for both treatments. Lack of somatic growth of these implants require multiple surgical interventions in case of pediatric patients. Advent of stem cell research and regenerative therapy propose an alternative and potential tissue engineered heart valves (TEHV) treatment approach to treat this life threatening condition. TEHV has the potential to promote tissue growth by replacing and regenerating a functional native valve. Hemodynamics play a crucial role in heart valve tissue formation and sustained performance. The focus of this study was to understand the role of physiological shear stress and flexure effects on de novo HV tissue formation as well as resulting gene and protein expression. A bioreactor system was used to generate physiological shear stress and cyclic flexure. Human bone marrow mesenchymal stem cell derived tissue constructs were exposed to native valve-like physiological condition. Responses of these tissue constructs to the valve-relevant stress states along with gene and protein expression were investigated after 22 days of tissue culture. We conclude that the combination of steady flow and cyclic flexure helps support engineered tissue formation by the co-existence of both OSS and appreciable shear stress magnitudes, and potentially augment valvular gene and protein expression when both parameters are in the physiological range.