Cardiovascular diseases (CVDs) are the leading cause of death and disability worldwide. The aging population and the rapidly increasing prevalence of obesity and type 2 diabetes will contribute to a growing epidemic of CVDs globally. Despite the extensive investigations in etiology, the pathogenesis of CVDs still not fully understand, and the treatment and prevention for CVDs are still limited. Significant interest has been raised in gut microbiota-host interaction since increasing evidence revealed that gut microbiomes play an important role in human health and diseases, including CVDs. Among more than two thousand gut microbiota metabolites, a compound named trimethylamine N-oxide (TMAO) was revealed to be closely related to CVDs. However, the impact of TMAO on cardiovascular health is still full of controversy and the direct impact of TMAO on heart tissue and cardiomyocytes has not been fully understood yet. In the first chapter, we reviewed the literature on TMAO-related atherosclerosis and cardiomyopathy to give us a general aspect of current research progress in the role of TMAO on CVDs. In this context, we provide an overview of the potential mechanisms underlying TMAO-induced cardiovascular diseases at the cellular and molecular levels, with a focus on atherosclerosis and cardiomyopathy. We also address the direct effects of TMAO on cardiomyocytes (a new and under-researched area) and finally propose TMAO as a potential biomarker and/or therapeutic target for the diagnosis and treatment of patients with CVDs. In the second chapter, the direct impact of TMAO on cardiac function was tested in vivo using wild-type C57B6L mice model. Four experiment groups were enrolled in the feeding protocol, which included 3w (different time points), 6w, and 13w feeding time to reveal the impact of short and longer periods of TMAO consumption on cardiac function. The plasma TMAO was measured by liquid chromatography-tandem mass spectrometry (LC/MS/MS) method at the end of the feeding protocol. Echocardiography and electrocardiography (ECG) were performed to assess the overall heart function. The histopathology staining was used to evaluate the cardiac microstructure change. By the end of the feeding protocol, the plasma TMAO all increased significantly in the TMAO group compared to the control no matter the TMAO feeding period. Echocardiography showed that 6w and 13w TMAO intake could significantly decrease cardiac contractility evidenced by decreased eject fraction (EF) and fraction shortening (FS). The electrocardiography (ECG) showed decreased R wave aptitude in 6w and 13w TMAO feed group with sinus rhythm. However, 3w TMAO intake had no impact on both cardiac contractability and ECG. Moreover, chronic TMAO supplement (13w) showed increased left ventricle (LV) mass on echocardiography and increased LV thickness on the tissue section. Further histology analysis revealed cardiomyocyte hypertrophy in the 13w TMAO-treated male group. Notably, the female mice showed significantly higher TMAO levels both in the control and treated group compared to the male, however, no gender difference was observed as to the ECG and echocardiography. In addition, the plasma inflammation cytokines were also analyzed and the tumor necrosis factor-α (TNF- α), interleukin 10 (IL-10), Fibroblast growth factor 2 (FGF β) and leptin were all increased in the 13w TMAO treated group compared to the control. These results suggest that chronic TMAO exposure led to increased plasma TMAO levels, which contribute to system inflammation and cardiac dysfunction due to cardiac hypertrophy in mice models. Research in chapter 3 demonstrates the potential underlying mechanisms of TMAO-induced cardiac dysfunction using adult mouse cardiomyocytes. In this study, we examined the direct effect of TMAO on reactive oxidative species (ROS) generation and factors related to cardiomyocyte contractibility, including, microtubule, Connexin43 (Cx43) expression, and gap junction intracellular communication (GJIC), intracellular calcium dynamics and transversal-tubule (T-tubule) both in acute and chronic TMAO challenge. Moreover, we also tested whether TMAO can enter cardiomyocytes directly. The results suggested that TMAO could enter cardiomyocytes through organic cation transporters (OCTs) and promote increased ROS generation via augmentation of NADPH oxidase 4 (Nox4). Moreover, both acute and chronic TMAO exposure could induce microtubule densification, which plays a critical role in intracellular protein transportation and cardiomyocyte morphology maintenance. We also demonstrated chronic TMAO exposure could inhibit the Cx43 expression at both cellular and tissue level, and therefore impact the GJIC for the first time. Besides, we also revealed that TMAO could interrupt intracellular calcium handling both acutely and chronically, especially documented by decreased efficiency in intracellular calcium removal, related to decreased sarcoplasmic reticulum Ca2+-ATPase (Serca2) expression. However, TMAO showed no impact on cardiomyocyte T-tubule network organization. Taken together, we demonstrated a direct destructive role of TMAO on cardiomyocytes' functional properties and provided a novel potential mechanism for TMAO-induced cardiac dysfunction. Overall, the research in this dissertation demonstrated the direct impact of TMAO on cardiomyocytes and cardiac function both in vivo and in vitro and evaluated the effect of TMAO both acutely and chronically. The TMAO can enter cardiomyocytes and induce Nox4-mediated oxidative stress, which could connect to multiple intracellular pathways, including microtubule densification, decreased Cx43 expression, and GJIC, as well as calcium handling dysfunction. Meanwhile, all these changes were closely related to the cardiomyocyte swelling observed in mice cardiac tissue after chronic TMAO consumption, which could ultimately contribute to cardiac contractile dysfunction and electrophysiology change in mice models. / Doctor of Philosophy / Cardiovascular diseases (CVDs) are a group of diseases related to our heart and blood vessels, such as heart attack and stroke. It is the leading cause of death and disability around the world, more common than diabetes and cancer. According to the reports of the American Heart Association, CVDs cost America 555 billion US dollars in 2016 while by 2035, the cost will reach 1.1 trillion. The individual, population, and economic impact of CVDs are tremendous, making CVD one of the largest public health problems at present. Despite the extensive investigations into the cause of CVDs, the exact underlying reason still not fully understand. The microbiome inside our body has raised much attention recently due to its close relationship with human health, including CVDs. The microbiome from the gut can affect our heart health both by affecting the immune system and its metabolites after we eat daily foods. Among thousands of metabolites, one named trimethylamine N-oxide (TMAO) has been shown to be related to increased CVDs risks. After we eat choline-rich food such as red meat and eggs, the gut microbiome can use these nutrients and produce TMA as metabolite waste, the TMA then goes into the liver and convert to TMAO via liver enzymes. However, the impact of TMAO on cardiovascular health is not fully understood yet. Our study uses the mice model to test whether TMAO has a direct impact on heat cells and heart function. We fed the mice with water containing 0.12% TMAO for different times including 3w, 6w, and 13w, and then check the mice's heart function through heart ultrasound and ECG. The results showed that TMAO could significantly harm heart function after long-term exposure in mice (13w). Further histology analysis of heart tissue showed increased heart cell size, which may contribute to decreased heart function. Certain blood inflammation cytokines related to CVDs also increased. The experiments using isolated mice heart cells showed that the ROS, which could harm the heart cells and related to lots of other damage processes in human health, were increased after exposure to the TMAO. Several other factors, including cell skeleton, cell channels responsible for cell-to-cell communication, and cell calcium balance were all damaged by TMAO, which could finally induce heart damage and heart diseases.

Because the many physicians and students of heredity have not been closely associated in finding that the causes of cardiovascular diseases might lie, in a large measure, to an inherited predisposition, this study has been undertaken; first, to contribute to several more case studies of cardiovascular diseases to the knowledge of heredity; second, to find if there is a possible successive occurrence of cardiovascular diseases in generation after generation; and third, to determine a possible mode of transmission from parents to offspring by an analysis of nine genealogies.

Yes / This study aimed to explore the challenges and barriers faced by staff involved in the delivery of the National Health Service (NHS) Health Check, a systematic cardiovascular disease (CVD) risk assessment and management program in primary care. Data have been derived from three qualitative evaluations that were conducted in 25 General Practices and involved in depth interviews with 58 staff involved all levels of the delivery of the Health Checks. Analysis of the data was undertaken using the framework approach and findings are reported within the context of research and practice considerations. Findings indicated that there is no ‘one size fits all’ blueprint for maximising uptake although success factors were identified: evolution of the programme over time in response to local needs to suit the particular characteristics of the patient population; individual staff characteristics such as being proactive, enthusiastic and having specific responsibility; a supportive team. Training was clearly identified as an area that needed addressing and practitioners would benefit from CVD specific baseline training and refresher courses to keep them up to date with recent developments in the area. However there were other external factors that impinged on an individual’s ability to provide an effective service, some of these were outside the control of individuals and included cutbacks in referral services, insufficient space to run clinics or general awareness of the Health Checks amongst patients. The everyday experiences of practitioners who participated in this study suggest that overall, Health Check is perceived as a worthwhile exercise. But, organisational and structural barriers need to be addressed. We also recommend that clear referral pathways be in place so staff can refer patients to appropriate services (healthy eating sessions, smoking cessation, and exercise referrals). Local authorities need to support initiatives that enable data sharing and linkage so that GP Practices are informed when patients take up services such as smoking cessation or alcohol harm reduction programmes run by social services.

Yes / Primary health care (PHC) physicians' perceptions are vital to understand as they are the first-line health care providers in cardiovascular diseases (CVD) risk assessment and management. This study aims to explore PHC physicians' perceptions on their roles and their perceptions on management and risk reduction approaches on CVD risk reduction and management in Fiji. This is a qualitative study conducted in the Suva Medical area among 7 health centers from 1 August to 31 September, 2021. Purposive sampling was used to recruit physicians who worked in the Suva medical area as PHC physicians with at least 6 months' experience in the Special Outpatients Department clinics. In-depth interview were conducted using a semi-structured questionnaire over the telephone and recorded on a tablet device application. The interview content was then transcribed, and thematic analysis was done. This study included 25 PHC physicians. From the thematic analysis, 2 major themes emerged with 6 subthemes. Theme 1 was CVD management skills with 3 subthemes including education, experience and trainings, beliefs and attitudes of physicians, self-confidence and effectiveness in CVD risk reduction and management. Theme 2 was roles and expectations with 3 subthemes including perceptions of effective treatment, perceptions of physicians' roles and perceptions of patients' expectations. Physicians generally see their role as central and imperative. They perceive to be important and leading toward combating CVDs. Physicians' perceptions on their commitment to prevention and management of CVDs through their skills and knowledge, beliefs and motivation should be acknowledged. It is recommended that the physicians are updated on the current evidence-based medicine. Limitations include results that may not be the reflection of the entire physician and multidisciplinary community and the difficulties in face-to-face interviews due to the coronavirus diseases of 2019 pandemic.

Thesis (M.P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 2008. / Source: Masters Abstracts International, Volume: 46-05, page: 2672. Adviser: Wendell C. Taylor. Includes bibliographical references.

Thesis (doctoral)--Institute of Dentistry, University of Helsinki, 2003. / Includes bibliographical references.

Thesis (Ph.D. in Nursing) -- University of Colorado Denver, 2008. / Typescript. Includes bibliographical references (leaves 194-203). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Xu Liying. / "April 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 159-175) / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.