Wong Cheuk Ying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (leaves 101-124). / Abstracts in English and Chinese. / Abstract --- p.i / 摘要 --- p.iv / Acknowledgement --- p.vi / List of Abbreviations --- p.vii / Chapter Chapter 1. --- General Introduction --- p.1 / Chapter Chapter 2. --- Methods --- p.4 / Chapter 2.1 --- Measurement of cAMP and cGMP in VSMCs --- p.4 / Chapter 2.1.1 --- Cell culture --- p.4 / Chapter 2.1.2 --- Enzyme-immunoassay colorimetric measurement for cAMP and cGMP --- p.5 / Chapter 2.1.3 --- Statistical analysis --- p.6 / Chapter 2.2 --- Measurement of apoptosis in VSMCs and bone marrow-derived stem cells --- p.6 / Chapter 2.2.1 --- Cell culture --- p.6 / Chapter 2.2.2 --- Hoechst33258 --- p.7 / Chapter 2.2.3 --- Cell Death ELISA plus --- p.7 / Chapter 2.2.4 --- Protein extraction and Western blot analysis of PKG expression --- p.8 / Chapter 2.2.5 --- Statistical analysis --- p.9 / Chapter 2.3 --- Measurement of cell proliferation in VSMCs and bone marrow-derived stem cells --- p.9 / Chapter 2.3.1 --- Cell culture --- p.9 / Chapter 2.3.2 --- Cell count --- p.10 / Chapter 2.3.3 --- MTT assay --- p.11 / Chapter 2.3.4 --- BrdU-(5`Bromo-2-deoxyuridine) ELISA colorimetric assay --- p.11 / Chapter 2.3.5 --- Statistical analysis --- p.12 / Chapter Chapter 3. --- Effects of hyperglycemia on CGRP-induced cAMP response in VSMCs / Chapter 3.1 --- Introduction --- p.13 / Chapter 3.2 --- Results --- p.18 / Chapter 3.3 --- Discussion --- p.22 / Chapter Chapter 4. --- Role of cGMP and protein kinase G in regulation of apoptosis in VSMCs / Chapter 4.1 --- Introduction --- p.26 / Chapter 4.2 --- Results --- p.30 / Chapter 4.3 --- Discussion --- p.44 / Chapter Chapter 5. --- Role of protein kinase G in regulation of proliferation in VSMCs / Chapter 5.1 --- Introduction --- p.55 / Chapter 5.2 --- Results --- p.58 / Chapter 5.3 --- Discussion --- p.67 / Chapter Chapter 6. --- Effects of aging and eNOS- and iNOS-gene deletion (using eNOS- and iNOS-knockout mice) on apoptosis of VSMCs / Chapter 6.1 --- Introduction --- p.73 / Chapter 6.2 --- Results --- p.76 / Chapter 6.3 --- Discussion --- p.79 / Chapter Chapter 7. --- Role of protein kinase G in regulation of apoptosis and proliferation of bone marrow stromal stem cells / Chapter 7.1 --- Introduction --- p.81 / Chapter 7.2 --- Results --- p.84 / Chapter 7.3 --- Discussion --- p.92 / Chapter Chapter 8. --- Overall discussion --- p.95 / Chapter Chapter 9. --- References --- p.101

Wenhong Wang. / "December 2003." / Description based on full citation and abstract (viewed May 20, 2006) / Thesis (Ph.D.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (p. 125-143). / 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.

Chan, Po Tai. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 128-150). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese; some appendixes in Chinese.

Numerous studies focusing on cardiovascular disease risk factors such as obesity, hypertension, smoking, diabetes mellitus, elevated serum lipids, inactivity and lack of physical fitness prevalent in children highlight the importance of the early diagnosis and prevention of conditions that are associated in adulthood with cardiovascular disease. The purpose of this study was to assess the impact of accumulative physical activity on the fitness profile, blood pressure and body composition in 14-16 year old school children in the Western Cape of South Africa.

Dados sobre a avaliação não invasiva da rigidez vascular e suas relações com variáveis de risco cardiovascular são escassos em jovens. Objetiva avaliar a relação entre a velocidade de onda de pulso (VOP) e a pressão arterial (PA), variáveis antropométricas, metabólicas, inflamatórias e de disfunção endotelial em indivíduos adultos jovens. Foram estudados 96 indivíduos (51 homens) do Estudo do Rio de Janeiro, em duas avaliações, A1 e A2, com intervalo de 17,691,58 anos (16 a 21 anos). Em A1 foram avaliados em suas escolas (10-15 anos - média 12,421,47 anos) e em A2 foram novamente avaliados em nível ambulatorial (26-35 anos - média 30,091,92 anos). Em A1 foram obtidos pressão arterial (PA) e índice de massa corporal (IMC). Em A2 foram obtidos a velocidade da onda de pulso (VOP)-método Complior, PA, IMC, circunferência abdominal (CA), glicose, perfil lipídico, leptina, insulina, adiponectina, o índice de resistência à insulina HOMA-IR, proteína C-Reativa ultrassensível (PCRus) e as moléculas de adesão E-selectina, Vascular Cell Adhesion Molecule-1(VCAM-1) e Intercellular Adhesion Molecule-1 (ICAM-1). Foram obtidos, ainda, a variação da PA e do IMC entre as 2 avaliações. Em A2 os indivíduos foram estratificados segundo o tercil da VOP para cada sexo. Como resultados temos: 1) Os grupos foram constituídos da seguinte forma: Tercil 1:homens com VOP < 8,69 m/s e mulheres com VOP < 7,66 m/s; Tercil 2: homens com VOP &#8805; 8,69 m/s e < 9,65m/s e mulheres com VOP &#8805; 7,66 m/s e < 8,31m/s;Tercil 3:homens com VOP &#8805; 9,65 m/s e mulheres com VOP &#8805; 8,31 m/s. 2) O grupo com maior tercil de VOP mostrou maiores médias de PA sistólica (PAS) (p=0,005), PA diastólica (PAD) (p=0,007), PA média (PAM) (p=0,004), variação da PAD (p=0,032), variação da PAM (p=0,003), IMC (p=0,046), variação do IMC (p=0,020), insulina (p=0,019), HOMA-IR (p=0,021), E-selectina (p=0,032) e menores médias de adiponectina (p=0,016), além de maiores prevalências de diabetes mellitus/intolerância à glicose (p=0,022) e hiperinsulinemia (p=0,038); 3) Houve correlação significativa e positiva da VOP com PAS (p<0,001), PAD (p<0,001), PP (p=0,048) e PAM (p<0,001) de A2, com a variação da pressão arterial (PAS, PAD e PAM) (p<0,001) entre as duas avaliações, com o IMC de A2 (p=0,005) e com a variação do IMC (p<0,001) entre as duas avaliações, com CA (p=0,001), LDLcolesterol (p=0,049) e E-selectina (p<0,001) e correlação negativa com HDLcolesterol (p<0,001) e adiponectina (p<0,001); 4)Em modelo de regressão múltipla, após ajuste do HDL-colesterol, LDLcolesterol e adiponectina para sexo, idade, IMC e PAM, apenas o sexo masculino e a PAM mantiveram correlação significativa com a VOP. A VOP em adultos jovens mostrou relação significativa com variáveis de risco cardiovascular, destacando-se o sexo masculino e a PAM como importantes variáveis no seu determinismo. Os achados sugerem que a medida da VOP pode ser útil para a identificação do acometimento vascular nessa faixa etária. / Data on non-invasive evaluation of vascular stiffness in the young and its relationship with cardiovascular (CV) risk variables are scarce. Objective to assess the relationship between pulse wave velocity (PWV) and blood pressure (BP), anthropometric, metabolic, inflammatory and endothelial dysfunction variables in young adults. Ninety-six individuals (51 males) from The Rio de Janeiro Study cohort were studied in two evaluations, A1 and A2, with an interval of 17.69 1.58 years (16-21 years). In A 1 they were evaluated at their schools (10-15 years average 12.42 1.47 years) and in A2 they were all re-evaluated as outpatients (26-35 years - average 30.09 1.92 years). In A1 BP and body mass index (BMI) were obtained. In A2 pulse wave velocity (PWV) by Complior method, BP, BMI, waist circumference (WC), glucose, lipid profile, leptin, insulin, adiponectin, the HOMA-IR insulin resistance index, high sensitive C-Reactive protein (CRPhs) and E-selectin, Vascular Cell Adhesion Molecule 1 (VCAM-1) and Intercellular Adhesion Molecule 1 (ICAM-1) adhesion molecules were obtained. The BP and BMI variation over the time interval between the two evaluations were also obtained. Subjects were stratified according to tertile of PWV for each sex in A2. As results: 1) The groups were constituted as follows: Tertile 1: males with PWV <8.69 m/s and females with PWV <7.66 m/s; Tertile 2: males with PWV &#8805; 8.69 m/s and <9.65 m/s and females with PWV &#8805; 7.66 m/s and <8.31 m/s; Tertile 3: males with PWV &#8805; 9.65 m/s and females with PWV &#8805; 8.31 m/s 2) The group with the highest PWV tertile showed higher values of systolic BP (SBP) (p=0.005), diastolic BP (DBP) (p=0.007), mean BP (MBP) (p=0,004), DBP variation (p=0,032), MBP variation (p=0.033), BMI (p=0.046), BMI variation (p=0.020), insulin (p=0.019), HOMA-IR (p=0.021), E-Selectin (p=0.032) and lower values of adiponectin (p=0.016), besides higher prevalence of diabetes mellitus/glucose intolerance (p=0.022) and hyperinsulinemia (p=0.038); 3) There were a significant positive correlation of PWV with SBP (p<0,001), DBP (p<0,001), PP (p=0,048) and MBP (p<0,001) from A2, variation in blood pressure (SBP, DBP, and MBP) (p<0,001) between the two assessments, BMI (p=0.005) and BMI variation between the two evaluations (p<0,001), WC (p=0.001), LDL-cholesterol (0.049), and E-selectin (p<0,001) and negative correlation with HDL-cholesterol (p<0,001) and adiponectin (p<0,001); 4) In the multiple regression model, HDL-cholesterol, LDL-cholesterol and adiponectin lost statistical significance after adjustment for sex, age, BMI and MBP, only the male gender and MBP remained significantly correlated with PWV. PWV in young adults showed a significant association with CV risk variables, highlighting the male gender and MBP as important variables in its determining. The findings suggest that measurement of PWV can be useful for the identification of vascular impairment in this age group.

Dados sobre a avaliação não invasiva da rigidez vascular e suas relações com variáveis de risco cardiovascular são escassos em jovens. Objetiva avaliar a relação entre a velocidade de onda de pulso (VOP) e a pressão arterial (PA), variáveis antropométricas, metabólicas, inflamatórias e de disfunção endotelial em indivíduos adultos jovens. Foram estudados 96 indivíduos (51 homens) do Estudo do Rio de Janeiro, em duas avaliações, A1 e A2, com intervalo de 17,691,58 anos (16 a 21 anos). Em A1 foram avaliados em suas escolas (10-15 anos - média 12,421,47 anos) e em A2 foram novamente avaliados em nível ambulatorial (26-35 anos - média 30,091,92 anos). Em A1 foram obtidos pressão arterial (PA) e índice de massa corporal (IMC). Em A2 foram obtidos a velocidade da onda de pulso (VOP)-método Complior, PA, IMC, circunferência abdominal (CA), glicose, perfil lipídico, leptina, insulina, adiponectina, o índice de resistência à insulina HOMA-IR, proteína C-Reativa ultrassensível (PCRus) e as moléculas de adesão E-selectina, Vascular Cell Adhesion Molecule-1(VCAM-1) e Intercellular Adhesion Molecule-1 (ICAM-1). Foram obtidos, ainda, a variação da PA e do IMC entre as 2 avaliações. Em A2 os indivíduos foram estratificados segundo o tercil da VOP para cada sexo. Como resultados temos: 1) Os grupos foram constituídos da seguinte forma: Tercil 1:homens com VOP < 8,69 m/s e mulheres com VOP < 7,66 m/s; Tercil 2: homens com VOP &#8805; 8,69 m/s e < 9,65m/s e mulheres com VOP &#8805; 7,66 m/s e < 8,31m/s;Tercil 3:homens com VOP &#8805; 9,65 m/s e mulheres com VOP &#8805; 8,31 m/s. 2) O grupo com maior tercil de VOP mostrou maiores médias de PA sistólica (PAS) (p=0,005), PA diastólica (PAD) (p=0,007), PA média (PAM) (p=0,004), variação da PAD (p=0,032), variação da PAM (p=0,003), IMC (p=0,046), variação do IMC (p=0,020), insulina (p=0,019), HOMA-IR (p=0,021), E-selectina (p=0,032) e menores médias de adiponectina (p=0,016), além de maiores prevalências de diabetes mellitus/intolerância à glicose (p=0,022) e hiperinsulinemia (p=0,038); 3) Houve correlação significativa e positiva da VOP com PAS (p<0,001), PAD (p<0,001), PP (p=0,048) e PAM (p<0,001) de A2, com a variação da pressão arterial (PAS, PAD e PAM) (p<0,001) entre as duas avaliações, com o IMC de A2 (p=0,005) e com a variação do IMC (p<0,001) entre as duas avaliações, com CA (p=0,001), LDLcolesterol (p=0,049) e E-selectina (p<0,001) e correlação negativa com HDLcolesterol (p<0,001) e adiponectina (p<0,001); 4)Em modelo de regressão múltipla, após ajuste do HDL-colesterol, LDLcolesterol e adiponectina para sexo, idade, IMC e PAM, apenas o sexo masculino e a PAM mantiveram correlação significativa com a VOP. A VOP em adultos jovens mostrou relação significativa com variáveis de risco cardiovascular, destacando-se o sexo masculino e a PAM como importantes variáveis no seu determinismo. Os achados sugerem que a medida da VOP pode ser útil para a identificação do acometimento vascular nessa faixa etária. / Data on non-invasive evaluation of vascular stiffness in the young and its relationship with cardiovascular (CV) risk variables are scarce. Objective to assess the relationship between pulse wave velocity (PWV) and blood pressure (BP), anthropometric, metabolic, inflammatory and endothelial dysfunction variables in young adults. Ninety-six individuals (51 males) from The Rio de Janeiro Study cohort were studied in two evaluations, A1 and A2, with an interval of 17.69 1.58 years (16-21 years). In A 1 they were evaluated at their schools (10-15 years average 12.42 1.47 years) and in A2 they were all re-evaluated as outpatients (26-35 years - average 30.09 1.92 years). In A1 BP and body mass index (BMI) were obtained. In A2 pulse wave velocity (PWV) by Complior method, BP, BMI, waist circumference (WC), glucose, lipid profile, leptin, insulin, adiponectin, the HOMA-IR insulin resistance index, high sensitive C-Reactive protein (CRPhs) and E-selectin, Vascular Cell Adhesion Molecule 1 (VCAM-1) and Intercellular Adhesion Molecule 1 (ICAM-1) adhesion molecules were obtained. The BP and BMI variation over the time interval between the two evaluations were also obtained. Subjects were stratified according to tertile of PWV for each sex in A2. As results: 1) The groups were constituted as follows: Tertile 1: males with PWV <8.69 m/s and females with PWV <7.66 m/s; Tertile 2: males with PWV &#8805; 8.69 m/s and <9.65 m/s and females with PWV &#8805; 7.66 m/s and <8.31 m/s; Tertile 3: males with PWV &#8805; 9.65 m/s and females with PWV &#8805; 8.31 m/s 2) The group with the highest PWV tertile showed higher values of systolic BP (SBP) (p=0.005), diastolic BP (DBP) (p=0.007), mean BP (MBP) (p=0,004), DBP variation (p=0,032), MBP variation (p=0.033), BMI (p=0.046), BMI variation (p=0.020), insulin (p=0.019), HOMA-IR (p=0.021), E-Selectin (p=0.032) and lower values of adiponectin (p=0.016), besides higher prevalence of diabetes mellitus/glucose intolerance (p=0.022) and hyperinsulinemia (p=0.038); 3) There were a significant positive correlation of PWV with SBP (p<0,001), DBP (p<0,001), PP (p=0,048) and MBP (p<0,001) from A2, variation in blood pressure (SBP, DBP, and MBP) (p<0,001) between the two assessments, BMI (p=0.005) and BMI variation between the two evaluations (p<0,001), WC (p=0.001), LDL-cholesterol (0.049), and E-selectin (p<0,001) and negative correlation with HDL-cholesterol (p<0,001) and adiponectin (p<0,001); 4) In the multiple regression model, HDL-cholesterol, LDL-cholesterol and adiponectin lost statistical significance after adjustment for sex, age, BMI and MBP, only the male gender and MBP remained significantly correlated with PWV. PWV in young adults showed a significant association with CV risk variables, highlighting the male gender and MBP as important variables in its determining. The findings suggest that measurement of PWV can be useful for the identification of vascular impairment in this age group.

Introduction – Objectives. The cardiovascular system is in direct and constant interaction with its environment. Exposure to various environmental parameters, such as low temperature, air pollution and tobacco smoke, has been strongly associated with serious or even fatal cardiovascular outcomes. Arterial stiffening and greater wave reflection are age-related vascular modifications that lead to an increased risk of cardiovascular events. The aim of this work was to explore the relationship between selected environmental factors and arterial elastic properties in an effort to elucidate the underlying mechanisms that link these factors to increased cardiovascular mortality.<p><p>Study 1: Effects of cold exposure on central and peripheral vascular tone. Our first study explored the effects of cold exposure on aortic stiffness and peripheral microvascular tone. We observed that cold exposure, in addition to its chronotropic effects, provoked an increase in aortic stiffness, as assessed by aortic pulse wave velocity, as well as significant vasoconstriction of peripheral arterioles in the microcirculation. Moreover, we explored the magnitude of this effect in a different population (Black subjects of African origin), which is traditionally characterized by exaggerated reactions to adrenergic stimuli. We noted that the vascular reactions, in terms of both aortic stiffness and microvascular vasoconstriction, were more profound in Black Africans than in age-matched Caucasian-Whites. These results argue for a direct effect of cold exposure on arterial stiffness and peripheral vascular tone, probably through activation of the orthosympathetic system.<p><p>Study 2: Exposure to ambient particulate matter and arterial stiffness. We explored the effects of acute exposure to outdoor particulate matter on aortic stiffness and aortic wave reflection. We studied the relationship between central hemodynamic parameters and ambient concentration of particulate matter in a population of patients who attended the Hypertension Clinics of Athens University. After statistical correction for a number of potential confounders, we did not observe an association between ambient concentrations of particulate matter and aortic stiffness. However, in men, particulate matter concentration was related to the amplitude of the reflected wave reaching the aorta from the periphery. These results suggest a direct acute interaction between particulate matter concentration and vascular tone, leading to an enhanced arterial wave reflection.<p><p>Study 3: The role of nicotine on the vascular effects of environmental tobacco smoke. Environmental tobacco smoke is considered as the most important source of particulate matter in the indoor environment. We recently demonstrated that exposure to tobacco smoke augmented wave reflection, an effect that was not seen after equivalent exposure to the smoke of non-tobacco, herbal cigarettes. We also noticed that the increased wave reflection was proportional to the plasma concentrations of nicotine. However, a direct causal effect between nicotine, arterial wave reflection and aortic stiffness has never been clearly demonstrated. We observed that increasing nicotine plasma concentration to levels comparable to those seen after extensive exposure to environmental tobacco smoke, provoked an increase in both aortic stiffness and arterial wave reflection after correction for heart rate and blood pressure changes. These results confirm the significant participation of nicotine in the vascular effects of passive smoking.<p><p>Conclusions. Globally, our results reveal the deleterious effects of cold, particulate matter exposure, and nicotinic stimulation on arterial stiffness, peripheral microcirculation and aortic wave reflection. The hemodynamic modifications associated with these effects may at least partially explain the causal relation between cold exposure, ambient air pollution and cardiovascular mortality.<p><p>Introduction-Objectifs. Le système cardiovasculaire est en relation directe et constante avec l’environnement. L’exposition au froid, la pollution atmosphérique et le tabagisme passif sont associés à des événements cardiovasculaires aigus graves et même fatals. La rigidification des artères et l’intensification de la réflexion de l’onde de pouls au niveau de l’aorte accompagnent le vieillissement et prédisent un risque cardiovasculaire accru. Nous avons testés l’hypothèse que les effets cardiovasculaires délétères des facteurs environnementaux comportent une altération des propriétés élastiques artérielles. Ceci pourrait être un des mécanismes physiopathologiques qui lie la mortalité cardiovasculaire aux variables environnementales.<p><p>Étude 1 :Exposition au froid ;effets centraux et périphériques. Notre première étude portait sur l’effet de l’exposition au froid sur la rigidité aortique et le tonus vasculaire des artérioles périphériques. Nous avons démontré que l’exposition au froid, hormis ses effets chronotropes, provoquait une augmentation de la rigidité artérielle – mesuré par la vitesse de l’onde de pouls au niveau de l’aorte - ainsi qu’une vasoconstriction importante au niveau des artérioles de la microcirculation. Nous avons ensuite déterminé l’amplitude de cet effet dans une autre population (sujets Africains-Noirs) qui se caractérise par des réactions plus prononcées aux différentes stimulations adrénergiques. Nous avons observé que les réactions vasculaires, tant au niveau de la rigidité aortique qu’au niveau de la microcirculation, étaient plus marquées chez les Africains-Noirs que chez les Caucasiens. Ces résultats révèlent un effet délétère de l’exposition au froid sur la rigidité aortique et le tonus vasculaire des artères périphériques, probablement via une activation du système orthosympathique.<p><p>Étude 2 :Exposition aux microparticules atmosphériques et rigidité artérielle. Nous avons ensuite investigué les effets de la pollution atmosphérique sur la rigidité artérielle et la réflexion de l’onde de pouls vers l’aorte. Nous avons étudié la relation entre les paramètres hémodynamiques centraux et la concentration atmosphérique de microparticules dans une population de patients qui ont consulté la Clinique Universitaire d’Hypertension Artérielle d’Athènes. Après correction statistique pour les facteurs confondants, nous n’avons pas observé de corrélation entre la rigidité artérielle et le taux de microparticules atmosphériques dans l’ensemble de la population investiguée. Par contre, si on restreint l’analyse aux résultats obtenus chez les sujets masculins, on s’aperçoit que la concentration atmosphérique de microparticules était associée de façon significative avec l’amplitude de l’onde réfléchie par la périphérie vers l’aorte et la pression pulsée aortique. Ces résultants suggèrent un effet direct des microparticules au niveau de la microcirculation. L’augmentation de l’amplitude de l’onde réfléchie consécutive à une vasoconstriction périphérique, modifie vraisemblablement les pressions au niveau de l’aorte chez le sujet masculin lors de pics de pollution.<p><p>Etude 3 :Le rôle de la nicotine dans les effets vasculaires du tabagisme passif. Le tabagisme passif est considéré comme la source la plus importante d’émission de microparticules au niveau domestique. Cependant, la composition chimique des particules semble jouer un rôle essentiel sur les ondes de réflexion. Nous avons démontré récemment que l’exposition passive à la fumée des cigarettes du tabac augmente l’intensité de la réflexion de l’onde de pouls. Ceci n’a pas été observé avec l’exposition à la fumée des cigarettes non tabagiques, en dépit d’une concentration ambiante tout à fait comparable de microparticules. Par ailleurs, nous avons observé que l’augmentation de l’incidence de l’onde de pouls au niveau de l’aorte était fortement associée à la concentration plasmatique de la nicotine. Un lien causal entre la nicotine, réflexion de l’onde de pouls et rigidité artérielle n’avait jamais clairement été établi. Nous avons testé cette hypothèse en administrant la nicotine pure chez des sujets sains. Nous avons observé que l’augmentation des taux plasmatiques de la nicotine à des valeurs comparables à celles qui surviennent après une exposition intensive au tabagisme passif, intensifiait la réflexion de l’onde de pouls et augmentait la rigidité artérielle. La correction statistique pour l’augmentation de la fréquence cardiaque et l’augmentation de la pression artérielle en réponse à la nicotine ne modifiait pas ces conclusions. Nos résultats démontrent ainsi les effets cardiovasculaires importants de faibles concentrations de nicotine, similaires à ceux qui sont atteints en cas d’exposition à un tabagisme passif.<p><p>Conclusions. Nos résultats révèlent les effets néfastes de l’exposition au froid et aux microparticules atmosphériques sur la rigidité artérielle, la microcirculation périphérique et la réflexion de l’onde de pouls. Nous avons pu également démontrer le rôle de la stimulation nicotinique dans les effets vasculaires aigus du tabagisme passif, comme en témoigne l’augmentation de la réflexion de l’onde de pouls au niveau aortique. Ces modifications hémodynamiques favorisent l’ischémie myocardique, et constituent un des mécanismes par lesquels l’exposition au froid et à la pollution atmosphérique favorisent la pathologie cardiovasculaire.<p> / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

Les maladies chroniques (dont les maladies cardio-vasculaires (MCV)) constituent dans la majorité des pays en Europe voire dans le monde, une des principales causes de mortalité et de morbidité. En Belgique, ces pathologies sont responsables de 37% des décès (33% des décès chez les hommes et 40% chez les femmes) .<p><p>Les études épidémiologiques ont montré que certaines populations sont plus susceptibles que d’autres de développer ou de décéder des maladies cardio-vasculaires (1). Pendant longtemps, l’Europe a été caractérisée par des écarts importants de mortalité cardio-vasculaire entre le Nord, plus à risque, et le Sud. Ces différences entre populations s’expliquent par des facteurs génétiques, environnementaux, sociaux et culturels. <p><p>Parmi les facteurs culturels et environnementaux, des travaux scientifiques montrent, depuis plusieurs dizaines d’années, que l’alimentation et l’état nutritionnel participent de façon essentielle au développement et à l’expression clinique des maladies dans l’ensemble des pays industrialisés. Un équilibre nutritionnel, une consommation alimentaire variée, avec une répartition satisfaisante des quantités ingérées permettent de préserver un bon état de santé. <p><p>Les études épidémiologiques interethniques ont joué un rôle important dans l’avancée de la recherche de ces facteurs. Les études d’observation révèlent que lorsque des sujets d’un groupe ethnique particulier changent d’environnement, leur statut physique change au contact du nouvel environnement et diffère généralement de ceux restés dans le pays d’origine. La comparaison des taux de mortalité et de morbidité des immigrés de longue date aux taux observés dans le pays d’origine permet d’étudier la contribution des facteurs génétiques et environnementaux dans les variations de morbidité et de mortalité.<p><p>Les différences de morbidité et de mortalité entre ethnies ont été largement documentées pour les immigrés hispaniques, africains et sud-asiatiques en Amérique du Nord et en Grande Bretagne. Ces études ont montré que le profil de santé des immigrés est influencé tant par l’environnement du pays de naissance que par celui du pays d’accueil. L’influence de ces deux environnements peut donner lieu à 3 modèles de morbidité et de mortalité :la sous-mortalité (principalement observée parmi les immigrés de première génération issus de pays moins développés), la convergence (mortalité ou morbidité égale. Ce modèle concerne essentiellement les immigrés de seconde génération) et le dépassement (sur-mortalité ou sur-morbidité). <p><p>La santé des immigrés en Belgique est mal connue et peu étudiée. Dans la majorité des statistiques sanitaires comme dans les recherches épidémiologiques, les critères de nationalité et de naissance soit n'apparaissent pas du tout, soit ne font l'objet d'aucune analyse. L'occultation de ces variables a cependant pour conséquence de laisser dans l'ombre des indications précieuses pour la mise en œuvre de politiques de santé publique. <p><p>Bien que d’un intérêt évident en épidémiologie, les études interethniques posent un certain nombre de problèmes méthodologiques. Difficile à traiter, cette question n'en demeure pas moins essentielle à penser. <p> / Doctorat en Sciences de la santé publique / info:eu-repo/semantics/nonPublished

La prévention des maladies cardiovasculaires constitue actuellement une approche capitale dans la diminution de la mortalité au sein de nos pays industrialisés. Tous les facteurs de risques étant associés à une dysfonction endothéliale, nous nous sommes intéressés à deux classes de médicaments dont l’action bénéfique se situe, du moins en partie, au niveau de l’endothélium vasculaire :les inhibiteurs de l’enzyme de conversion de l’angiotensine (IECA) et les inhibiteurs de l’hydroxy-3-méthyl-3-glutaryl-Coenzyme A (HMG-CoA) réductase (statines).<p> Le présent travail contribue à l’étude in vitro des effets protecteurs vasculaires de l’administration chronique, chez le rat, de deux statines (la pravastatine et l’atorvastatine) vis-à-vis de la toxicité aiguë des LDL humaines oxydées et vis-à-vis de la tolérance à la nitroglycérine. Une comparaison est menée par rapport au ramipril dans ces deux modèles expérimentaux.<p>Les effets de ces médicaments se manifestent au niveau vasculaire par une amélioration de la disponibilité du NO. Toutefois, dans nos modèles, des mécanismes singulièrement différents ont été identifiés entre les agents étudiés :alors que le ramipril engendre une augmentation de l’expression de la eNOS, enzyme synthétisant le NO, les statines permettent une meilleure disponibilité de ce radical par un mécanisme post-traductionnel. Outre cette action, elles semblent agir directement sur des enzymes oxydatives comme les NAD(P)H oxydases.<p>Une action antioxydante des statines pourrait expliquer tous les effets observés, ce qui n’est pas le cas pour le ramipril. Vu que le stress oxydatif intervient dans tous les facteurs de risques cardiovasculaires, diverses perspectives cliniques sont envisagées afin d’améliorer l’approche thérapeutique de la maladie athéroscléreuse.<p> / Doctorat en sciences pharmaceutiques / info:eu-repo/semantics/nonPublished

The aim of this research project was to assess and compare cardiovascular disease (CVD) risk in black males and females from an urban, working population in the Makana (Grahamstown) region of the Eastern Cape, South Africa. Two-hundred and ninety one individuals (males: n = 143, females: n = 148) with a mean age of 42.6 (±8.1) years were voluntarily recruited from the greater urban Makana (Grahamstown) area. Eight Cardiovascular disease (CVD) risks were assessed: stature and mass were obtained in order to calculate body mass index (BMI) (mass/stature2). Obesity, defined as a morphological risk, was classified according to the World Health Organisation (WHO) BMI criteria (BMI>30kg.m-2), as well as according to measures of waist circumference (WC) and body composition. Hypertension, hypercholesterolemia and type II diabetes, were grouped as cardiovascular (CV) risks. Hypertension was defined as a blood pressure greater than 140/90mmHg (JNC-7); hypercholesterolemia, as total cholesterol greater than 6.2mmol.L-1 (NCEP); and type II diabetes, as total glucose greater than 12mmol.L-1 (WHO). Physical activity, diet, tobacco use, and alcohol consumption and dependence were grouped as lifestyle-related risks. These were assessed by means of self-reporting through the use of various validated questionnaires. Finally, self-reporting of obesity, hypertension, hypercholesterolemia and type II diabetes was assessed, in addition to perception questions on individuals’ perceived body shape and size (Ziebland figures). Self-reported and perceived responses were then compared to actual measures. Females were significantly (p<0.001) heavier than the males (92.7kg compared to 72.1kg) and had significantly (p<0.001) higher BMIs than their male counterparts (37.6kg.m-2 compared to 25.7 kg.-2). They also recorded significantly (p<0.001) higher waist circumference (WC) values and had significantly (p<0.001) higher percentage and total body fat. Significantly (p<0.001) more females were obese (81%) compared to males (17%). While a higher percentage of males (25 % compared to 22%) presented with stage I hypertension (≥140/90mmHg, <160/95mmHg), significantly (p<0.05) more females (14% compared to 8%) presented with stage II hypertension (>160/95mmHg). The prevalence of hypercholesterolemia at a high level of risk (>6.2mmol.L-1) was relatively low (2.1 % of males, 3.4% of females), but notably more participants (22% of males and 26% of females) presented with the condition at a moderate level of risk (>5mmol.L-1). Type II diabetes was the least prevalent CV risk factor, with no males and only 3% of females presenting with the condition. Males consumed significantly (p<0.05) more in terms of total energy intake (9024 vs. 7234 kJ) and were significantly (p<0.05) more active (3315 compared to 2660 MET-mins.week). A significantly (p<0.05) higher percentage of males smoked (51.1% compared to 3.4%), consumed alcohol (73.4% compared to 46.6%) and were alcohol dependent (40% compared to 33.5%). Both males and females tended to be ignorant of their health status, with both samples under-reporting obesity, hypertension and hypercholesterolemia, while over-reporting type II diabetes. Furthermore, obesity was significantly (p<0.05) underestimated, with both male and female individuals perceiving themselves to be notably smaller than they actually were. Physical activity and diet were important determinants of CVD risk in this black urban sample of individuals. Obesity, in particular central adiposity, was the most notable risk (particularly in females), followed by hypertension (particularly in males). Although some risks presented at a moderate level of risk, a clustering of risk factors was evident in both samples, with 12.6% and 41.2% of males and females presenting with two risk factors, and 2.8% and 8.1% of males and females respectively presenting with three risks.