Cardioselective Nitric Oxide Synthase Gene Transfer to Target Myocardial Ischemia


Book Description

This is a Ph.D. dissertation. Introduction: Cardiovascular and myocardial gene transfer, Gene delivery strategies to the cardiovascular system, Gene vector design, Adenovirus-mediated immunity and cardiovascular gene transfer, Myocardial gene transfer to target myocardial ischemia - reperfusion injury; Specific aims; Materials and methods: Construction of recombinant virus, Myocardial transfer and anti-adenoviral immunity, Gene transfer and myocardial ischemia-reperfusion injury, Statistical analysis; Results: Anti-adenoviral immunity and myocardial adenoviral gene transfer, Gene transfer and myocardial ischemia-reperfusion injury; Discussion: Pre-existing anti-adenoviral immunity and adenovirus-mediated myocardial gene transfer, Intramyocardial NOS3 gene transfer and adenovirus-mediated immune responses, Cardioselective NOS3 gene transfer and myocardial protection from reperfusion injury; General conclusions.













Fatty Acid Synthase


Book Description

Fatty acid synthase (FAS) is a key lipogenic enzyme catalyzing the terminal steps in the synthesis of fatty acids. In the majority of normal tissues, FAS expression is low. In many human cancers, however, including cancer of the prostate, FAS expression and FAS activity are very high. As shown in the laboratory, overexpression of FAS in tumor cells is part of a more general and coordinate upregulation of multiple lipogenic genes caused, at least in part, by activation of sterol regulatory element binding proteins (SREBPs), transcription factors that play a key role in cellular lipid homeostasis. The mechanisms underlying the activation of the SREBP pathway and the increase in lipogenesis in tumor cells as well as the ultimate biological significance of this phenomenon remain poorly understood. Nonetheless there is evidence that overexpression of lipogenic genes occurs early in tumor development and that the degree of overexpression correlates with increasing tumor grade. Moreover, a number of studies suggest that inhibition of FAS selectively reduces proliferation of tumor cells and causes apoptosis, implying that FAS and other lipogenic enzymes may constitute interesting targets for antineoplastic therapy.













Genetic Variation and Environmental Factors in Biological and Arterial Ageing


Book Description

Ageing, the decline in survival and bodily functions, caused by damage to macromolecules and tissues is intrinsically linked to life. Although universal and unavoidable, ageing does not occur in a uniform way. In the general population, it is actually a continuously distributed phenotype, in which genetic as well as environmental factors play an interactive role and explain the large interindividual differences between biological and chronological age. Cardiovascular disorders, which find there origins in deterioration of the structure and function of the large arteries, explain a large part of morbidity and mortality in industrialized societies. In this doctoral dissertation, the focus was on telomere length and arterial stiffness as biomarkers of biological and arterial ageing, respectively. It was investigated to what extent genetic and environmental determinants of oxidative stress and inflammation impact on the ageing process. Contents include: Introduction, Arterial ageing in cardiovascular risk prediction, Genetic and environmental factors in biological and arterial ageing, Telomere length and possible link to X chromosome, Role of smoking, oxidative stress and the -174 G/C interleukin-6 polymorphism in biological and vascular ageing, Environmental factors in arterial ageing, Blood pressure and blood selenium: a cross-sectional and a longitudinal population study, Endothelial function and outdoor temperature, General Discussion, Summary, Short Curriculum Vitae.