Cardiovascular disease is the leading cause of death globally. Chronic hypertension can lead to a gradual deterioration in the structure and performance of the cardiovascular system in a process described as cardiovascular remodelling. The ultimate response to this remodelling is heart failure. While cardiovascular remodelling is characterised by features such as cardiac and vascular hypertrophy, endothelial dysfunction and fibrosis; mechanisms leading to such pathologies are still unclear. However, oxidative stress, the damage caused by increased production of reactive oxygen species such as free radicals, or their reduced removal by anti-oxidants, appears to have a significant role. The major aim of this thesis is to investigate the involvement of reactive oxygen species in cardiovascular remodelling and to further investigate the potentials of three anti-oxidant approaches (a combination of alpha-lipoic acid and vitamin E, apocynin and a red-wine component, resveratrol) in preventing or reversing cardiovascular remodelling. These studies were conducted in two well-established rat models of cardiovascular remodelling including the deoxycorticosterone acetate (DOCA)-salt hypertensive rat and the ageing spontaneously hypertensive rat (SHR). Additionally, this thesis also characterises the effects of ovariectomy on the blood pressure and survival rate of female SHR. The cardiovascular structure and function in the animals have been defined using in vivo echocardiography, ex vivo isolated Langendorff heart perfusion, isolated thoracic aortic rings, histological analysis of the myocardial extracellular matrix and inflammation along with terminal organ weight measurements. Reactive oxygen species were assessed through the measurement of plasma malondialdehyde (MDA) while the anti-oxidant capacities have been assessed through measurements of plasma total anti-oxidant status (TAS) and plasma glutathione peroxidase (GPx) activity. DOCA-salt treated rats exhibited hypertension, oxidative stress and cardiovascular remodelling, evidenced by their increased left ventricular weights, excess collagen deposition in the heart and increased values for diastolic stiffness, increased plasma MDA concentrations along with impaired contraction and relaxation of the vessels. Treatment with a combination of alpha-lipoic acid and vitamin E or apocynin significantly inhibited the increases in blood pressure, left ventricular weights, cardiac stiffness, interstitial collagen deposition along with improvements in the vascular responses. The treatment of ageing male SHRs with resveratrol, although without any decrease in blood pressure, was shown to reduce left ventricular hypertrophy, fibrosis, diastolic stiffness and improve functional performance of the heart. The level of oxidative stress was also lowered in the male SHRs treated with resveratrol as evidenced by decreased plasma MDA and increased TAS. Female SHRs had a higher blood pressure and diastolic stiffness compared to their age-matched WKYs. Similar to male SHRs, treatment with resveratrol did not affect blood pressure, but attenuated the increased diastolic stiffness, in female SHRs. Furthermore, the ovariectomised SHRs were proven to be extremely hypertensive and had a significantly poorer survival rate. Overall, these studies demonstrated great potential for the alpha-lipoic acid and vitamin E combination and apocynin in the treatment of cardiovascular remodelling. However, further clinical and experimental research is essential to confirm the complete cardiovascular health benefits of resveratrol or red wine intake.

Title page, table of contents and summary only. The complete thesis in print form is available from the University of Adelaide Library. / The results presented in this thesis show the existence of TREK-1(Twik-RElated K+ channel; KCNK2), variant A and C of TREK-2 (KCNK10) and TRAAK (Twik-Related Arachidonic Acid-stimulated K+ channel; KCNK4) in human heart; the localization of TREK-1 and variants of TREK-2 on the membrane and in cytoplasmic areas of human cardiomyocyte; the notably high-level expression of TREK-1 in diseased human heart; the reverse expression of variant A and C of TREK-2 in normal and diseased human heart. These observations strongly indicate TREK channels play important roles in arrhythmia genesis and TREK-sensitive cardiac remodelling within the development of cardiac hypertrophy, ischemia cardiomyopathy and idiopathic dilated cardiomyopathy. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1248412 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2006

Cardiac hypertrophy is clinically defined as a relative increase in heart size associated with a thickening of the ventricular wall. It is a common feature of individuals suffering from different cardio-vascular or metabolic conditions and leads to heart failure. The structural, functional and molecular mechanisms which induce hypertrophy independent of hemodynamic alterations are poorly characterized. In this study, questions about whether cardiac-specific neuro-endocrine activation or metabolic imbalance are sufficient to induce hypertrophic structural and functional remodeling are addressed using genetically manipulated mouse models of primary cardiac hypertrophy. (For complete abstract open document)

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 6 uppsatser.

Thesis (Ph. D.)--University of Illinois at Chicago, 2004. / Includes bibliographical references (leaves 172-194). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (M.S.)--University of Missouri-Columbia, 2005. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "May 2005" Includes bibliographical references.

Thesis (Ph. D.)--University of Illinois at Chicago, 2004. / Includes bibliographical references (leaves 172-194).

A hipertrofia cardíaca é um dos principais mecanismos de adaptação do coração frente a uma sobrecarga de trabalho e pode advir de estímulos patológicos como a hipertensão arterial levando a um prejuízo funcional ou por estímulos fisiológicos como o treinamento físico que por outro lado, promove adaptações benéficas no coração. Na última década uma nova classe de moléculas, os miRNAs, vem sendo estudada como reguladores da expressão gênica em diversos tipos celulares, inclusive os cardiomiócitos. Entretanto, estudos sobre a participação de miRNAs nas adaptações induzidas pelo treinamento físico ainda são escassos. O presente trabalho teve como principal objetivo avaliar o efeito do treinamento físico aeróbio no perfil de expressão de miRNAs no coração de ratos espontaneamente hipertensos (SHR) bem como selecionar miRNAs com padrão alterado no SHR e revertido pelo treinamento físico e analisar seu papel funcional através de aplicativos de bioinformática. Os animais foram divididos em três grupos: ratos espontaneamente hipertensos sedentários (SHR-S), SHR treinados (SHR-T) e um grupo normotenso sedentário (WKY-S). O grupo SHR-T desempenhou um protocolo de treinamento de natação de 60 minutos, 5 vezes por semana durante 10 semanas e com um sobrecarga de 5% do peso corporal na cauda. Foram feitas análises hemodinâmicas (pressão arterial, PA e freqüência cardíaca de repouso, FC), funcionais (capacidade física, consumo de oxigênio, ecocardiograma), bioquímicas a expressão de miRNAs (microarray, Real Time-PCR) e computacionais (predição de alvos e anotação de vias de sinalização). Os principais resultados foram: 1. A PA e FC reduziu no grupo SHR-T em relação aos animais sedentários; 2. A capacidade de tolerância ao esforço, VO2 pico aumentou no grupo SHR-T; 3. Análise ecocardiográfica mostrou que a onda E, Onda A e razão E/A melhoram no grupo SHR-T. 4. Análise de microarray encontrou 6 diferentes padrões no perfil de expressão de miRNAs na comparação dos grupos WKY-S, SHR-S e SHR-T; 5. 6 miRNAs alterados no SHR-S tiveram sua expressão revertida no SHR-T (miR-1, 22, 27a, 27b, 29c e 451); 7. Análise bioinformática mostrou que esse grupo de miRNAs tem como alvo predito diversas vias de sinalização relacionados com o remodelamento cardíaco como MAPK, TGF-beta e Wnt, além de vias relacionadas com estrutura do citoesqueleto e metabolismo energético. Em conclusão, nossos resultados sugerem que os miRNAs: 1, 22, 27a, 27b, 29c e 451 podem estar governando vias de sinalização celular envolvidas no processos de reversão do quadro patológico. Esse fato abre novas perspectivas a respeito da utilização dessas moléculas como forma de terapias / Cardiac hypertrophy is a major mechanism of adaptation of the heart by the increased workload and may result from pathological stimuli such as high blood pressure leading to functional impairment or by physiological stimuli such as physical training, that on other hand promotes beneficial adaptations on the heart. In the last decade a new class of molecules, miRNAs, has been studied as regulators of gene expression in different cell type, including cardiomyocytes. However, few studies have investigated the miRNAs involved in adaptations to physical training. This study aimed to evaluate the effect of aerobic exercise training on expression profiling of miRNAs in the heart of spontaneously hypertensive rats (SHR) as well as select miRNAs with altered pattern in SHR and reversed by physical training and analyze their functional role through bioinformatics applications. The animals were divided into 3 groups: sedentary hypertensive rats (SHR-S), trained SHR (SHR-T) and sedentary Wistar Kyoto rats (WKY-S). The SHR-T group performed a swimming training protocol of 60 minutes, 5 times a week for 10 weeks and with overload of 5% of body weight in the tail. We analyzed hemodynamic (blood pressure, BP and resting heart rate, HR), functional (physical capacity, oxygen consumption and echocardiogram), biochemical (microarray and Real Time-PCR to miRNAs) and computational (prediction of targets and annotation cell signaling pathways) parameters. The main findings were: 1. The BP and HR decreased in SHR-T group compared to the sedentary animals; 2. The exercise tolerance and peak VO2 increased in SHR-T group; 3.Echocardiographic analysis showed that the E wave, A wave and E/A ratio improved in SHR-T group; 4. Microarray analysis found six different miRNAs expression profile in the comparison groups WKY-S, SHR-S and SHR-T; 5. Six miRNAs were altered in SHR-S and were reversed in the SHR-T (miR-1,22, 27a, 27b, 29c and 451); 7. Bioinformatics analysis showed that this miRNA cluster has multiple predicted targets in signaling pathways related to cardiac remodeling as MAPK, Wnt and TGF-beta and others genes associate to cytoskeletal structure and energetic metabolism. In conclusion, our results suggest that miRNAs: 1, 22, 27a, 27b, 29c and 451 can be controlling cell signaling pathways involved in the process of reversing the disease. These results open new perspectives on the use of these molecules as a therapeutic treatment

Esta dissertação trata das formas pelas quais um grupo de homens que frequentam uma academia de musculação da zona sul de Porto Alegre incorpora práticas de cuidados corporais com vistas à produção de corpos adequados aos padrões estéticos contemporâneos e como lidam com a ambiguidade decorrente destas práticas que se situam na fronteira entre o que é percebido como masculino e feminino. O marco teórico que subsidia este estudo contempla a discussão sobre masculinidades, as teorizações foucaultianas sobre biopolítica e os estudos sobre o governo dos corpos na contemporaneidade. O material empírico foi construído a partir de uma pesquisa de cunho etnográfico que conciliou observação participante e entrevistas semiestruturadas, cujos registros produziram um diário de campo. A análise consistiu em contrastar os achados da pesquisa com aqueles descritos na literatura, problematizando as formas pelas quais os frequentadores desta academia incorporam no seu cotidiano algumas práticas de cuidados com o corpo. Esse processo permitiu compreender que algumas práticas são consideradas não-problemáticas para a construção do gênero e são aceitas sem maiores problemas, enquanto outras, aquelas consideradas potencialmente perigosas para a afirmação da masculinidade, são modificadas ou suprimidas. / This paper is about a group of men that works out in a south Porto Alegre‟s gym and their body care and ways to achieve the contemporary esthetic patterns. The theoretical approach that bases this study faces the discussion about masculinities, foucaultians theories about biopolitics, and the studies about body government on contemporaneity and how they deal with the ambiguity resulting from such practices that are in the border of what is considerate masculine or feminine. Empiric material was build from an ethnographic research that matches observations of the participants and semi-structured interviews, whose records brought forth a research diary. Analyses consisted on contrast research results from those described on literature, problematizing the ways by which regulars from this gym incorporate in their everyday some body care practices. This process allowed comprehending that some practices are considered non-problematic for gender construction, and are commonly accept, whereas others, considered potentially danger for masculinity affirmation, are modified or suppressed.

Made available in DSpace on 2015-05-14T16:53:15Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-02-28Bitstream added on 2015-05-14T16:59:08Z : No. of bitstreams: 1 000816066.pdf: 8199814 bytes, checksum: 04f16c134dd5ae0397ebe390e2b76778 (MD5) / Uma vez iniciada a diálise, a sobrevida dos pacientes com doença renal crônica está diretamente relacionada às seguintes alterações cardiovasculares: hipertrofia ventricular esquerda) infarto agudo do miocãrdio, acidente vascular encefálico, arritmias cardíacas e hipertensão arterial. Dentre essas alterações encontradas em pacientes renais crônicos) merece destaque a hipertrofia ventricular esquerda. Desta forma) a reversão da hipertrofia ventricular esquerda tem potencial para interferir positivamente na sobrevida dos pacientes renais crônicos) tanto para as causas cardiovasculares como para mortalidade geral. O presente estudo teve como objetivo avaliar a influência da regressão da hipertrofia cardíaca na mortalidade cardiovascular dos pacientes em diálise e analisar a influência de variáveis clínicas sobre a regressão da hipertrofia ventricular esquerda. Foram analisados pacientes renais crônicos com idade superior a 18 anos) em programa de hemodiálise por 2 meses ou mais) antes da avaliação inicial; com dois ecocardiogramas no período de junho de 2000 a dezembro de 2008) seguidos até 2012; acompanhados no serviço de hemodiálise no Hospital das Clínicas de Botucatu-UNESP. Foram Excluídos os pacientes com evidência de discinesias ventriculares em ecocardiograma; doença valvar moderado ou grave; ecocardiografia de qualidade técnica insatisfatória; portadores de miocardiopatias de outras causas que não hipertensivas ou urêmicas; portadores de doenças com baixa expectativa de vida) quais sejam: neoplasias e cirrose hepática; e aqueles submetidos a transplante renal entre a primeira e a segunda avaliação. Os pacientes foram divididos em dois grupos: aqueles que mantiveram ou aumentaram a massa ventricular cardíaca e) aqueles que reduziram a massa ventricular cardíaca durante o seguimento. Observamos) em regressão múltipla de Cox, que a reversão da hipertrofia ventricular esquerda possui impacto na ... / Once started dialysis, the survival of patients with chronic kidney disease is directly related to cardiovascular changes, as following: left ventricular hypertrophy, myocardial infarction, stroke, cardiac arrhythmias and hypertension. Among these changes left ventricular hypertrophy is a common and powerful risk factor. In this way, reversal of left ventricular hypertrophy has potential to interfere positively with the survival of patients with renal disease, both for cardiovascular causes and for overall mortality. The present study aimed to evaluate the influence of regression of cardiac hypertrophy in cardiovascular mortality in dialysis patients and analyze the influence of clinical variables on the regression of left ventricular hypertrophy. Chronic kidney diseases patíents, aged over 18 years were analyzed, on hemodialysis for at least two months before the initial evaluation, from June 2000 to December 2008, and followed until 2012 in the hemodialysis service at the University Hospital of Botucatu-UNESP. The patients must have two echocardiograms. Were excluded patients with evidence of ventricular dyskinesia in echocardiogram, moderate or severe valvular disease, echocardiography with unsatisfactory technical quality; patients with cardiomyopathies due to causes other than hypertension or uremic; patients whose disease has a low life expectancy, which are: neoplasms and liver cirrhosis, and those undergoing kidney transplantation between the ftrst and second assessment. The patients were divided into two groups: those that maintained or increased the cardiac ventricular mass, and those that have reduced cardiac ventricular mass during follow-up. Multiple Cox regression was performed to evaluate the influence of reversal of left ventricular hypertrophy on mortality from cardiovascular causes. Over 6 years of follow-up, the survival curves of the two groups distanced themselves in a statistically signiftcant way. Reversal of left ...