published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Nursing Studies / Master / Master of Nursing in Advanced Practice

Despite major advances in pharmacological and surgical treatments of cardiovascular diseases (CVDs), clinical outcomes of patients with severe CVDs remain very poor. Most of medication and interventions currently available are only playing roles of preventing further damage to myocardium, declining the risk of on-going cardiovascular events, lifting the cardiac pumping efficiency and lower early mortality rates, none of these treatments can regenerate or repair damaged cardiac tissue or restore heart function. As a result, several new strategies have been explored to overcome limitations of current therapeutic approaches. One prospective is to replace dead cardiac vascular cells with young and green cells to repair or regenerate damaged heart myocardium. Several types of stem cells, including bone marrow hematopoietic stem cells, mesenchymal stem cells (MSCs), embryonic stem cell (ESCs)and induced pluripotent stem cells (iPSCs),have been tested as the candidates for treatment of CVDs. Among a myriad of types of stem cells, bone marrow derived MSCs(BM-MSCs) has received great attention based on several unique properties such as easy isolation and expansion, stable genetic background and low immunogenicity. However, the therapeutic efficacy of BM-MSCs derived from aging or diseased donors is impaired. The differentiation potential of BM-MSCs is gradually reduced with the increased culture time. Thus, it is urgent to identify some novel alternative sources for MSCs. Moreover, the potential mechanisms of MSCs therapy have not been understood totally. This thesis is designed to investigate the therapeutic efficacy and potential mechanisms of several novel types of MSCs, including hESC-MSCs and hiPSC-MSCs and Rap1-/--BM-MSCson several types of CVDs, including pulmonary arterial hypertension (PAH), dilated cardiomyopathy (DCM)and myocardial infarction (MI). In Chapter 4, it disclosed that hESC-MSCs have a better therapeutic efficacy than BM-MSCs in attenuation of PAH induced by monocrotaline in mice. The greater therapeutic potential of hESC-MSCs on PAH was not only attributed to the higher capacity of differentiation into de-novo vascular cells, but also attributed to higher cell survival rate and greater paracrine effects post-transplantation. In Chapter 5, it demonstrated that compared with BM-MSCs, iPSC-MSCs have a better therapeutic effect on doxorubicin-induced cardiomyopathy. Several potential mechanisms of action were involved in iPSC-MSCs-based therapy for cardiomyopathy. It demonstrated that iPSC-MSCs transplantation not only attenuated the generation of reactive oxygen species(ROS)and the level of inflammation, but also restored depletion of cardiac progenitor cells and promoted endogenous myocardial regeneration against doxorubicin induced cardiomyopathy. Moreover, mitochondrial transfer and paracrine actions of iPSC-MSCs played critical roles in the rescue for doxorubicin-induced cardiomyopathy. In Chapter 6, it uncovered that compared with wild type BM-MSCs,Rap1-/--BM-MSCs transplantation achieved a better benefit to MI induced by ligation of left anterior descending (LAD)coronary artery. Rap1-mediated NF-κB activity plays a key role in regulation MSCscytokine secretion profiles. The absence of Rap1 in MSCs leads to reduced pro-inflammatory cytokines secretion and enhanced MSCs survival capacity, thus yielding a better therapeutic efficacy. In conclusion, findings presented in this thesis provide important new insights regarding different novel types of MSCs, including those derived from ESC and iPSC. They have distinct mechanisms of action from BM-MSCs and provide superior therapeutic efficacy in various form of severe CVDs, including PAH and DCM. The safety and efficacy of these novel types of MSCs for treatment of CVDs deserve further investigations. / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

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The purpose of this research was to obtain information on the content of education within cardiac rehabilitation programs, methods of administering education, what the barriers are to providing education and which professionals administer education.To reach this goal, a questionnaire was modified from a previous study and a pilot study was undertaken to establish reliability of the questionnaire. The questionnaire was then sent to a sample of 100 directors of cardiac rehabilitation programs belonging to The American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR). The questionnaire focused on 13 established areas of education within cardiac rehabilitation programs.Once the questionnaires were completed, the information was transferred to a table format based upon the 13 content areas. The following conclusions were drawn from the research and the data gathered: 11 of the 13 content areas are offered at least 84% of the time, the major barriers for the 13 content areas were lack of time and lack of interest on the patient's behalf, the most frequent methods of education for all 13 content areas were individual education, print materials, and group education, and the primary educator overall for all 13 content areas was the nurse followed by the exercise physiologist and dietitian/nutritionist. / Department of Physiology and Health Science