Browsing by Subject "Cardiovascular disease"
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Item Embargo Diet-induced changes in mouse cells in vitro and in vivo zebrafish models of angiogenesis(Bilkent University, 2024-01) Yıldız, SelvinCardiovascular disorders rank as the primary cause of global mortality. Being overweight or obese impacts the pathogenesis of cardiovascular disease, resulting in an imbalance in endothelial function, cell growth, and inflammatory activation. Disruption of these factors resulting from endothelial cell dysfunction serves as both an outcome and a catalyst for vascular disease processes. Endothelial cells (ECs) are a natural barrier between circulating blood and vessel components. They also play critical roles in multiple physiological and pathophysiological processes, such as angiogenesis, vascular permeability, and inflammation. Amelioration of endothelial dysfunction may be attained by weight loss; however, complementary in vitro and in vivo studies are needed to establish the effects of weight loss on endothelial function and angiogenesis. This study developed an in vitro model to understand better the diet-induced changes in angiogenesis for mouse endothelial cells. In addition, a novel in vivo model of diet-induced vascular changes and its potential reversal with a return to regular diet in a zebrafish model was also studied. In vitro studies showed that a serum from mice fed a high-fat diet (HFD) might lead to proliferation of endothelial cells, yet weight loss did not compensate for prior stress induced by HFD. In vivo, studies in adult zebrafish showed that egg yolk-based high-fat diet might affect cytological architecture in the adult fish liver. Switching to a normal diet could effectively reverse these changes. Moreover, a caudal fin inter-ray vascularization assay was developed and used to test whether vessel sprouting was affected by different diets. Overfeeding resulted in a higher number of vessels, yet future studies with higher sample sizes are needed. Similarly, the expressions of several angiogenesis-related genes, which were quantified using cDNAs from the whole larvae and adult caudal fin treated with different diets, showed significant changes in vcam in larvae and cdh5 in adult fin by diet. However, further experiments are needed due to high individual variability and low sample size. The findings herein show that in vitro mouse endothelial cells and zebrafish larvae and adults could be used as valuable models for studies involving reversal/weight loss of high fat or overfeeding dietary regimes. Furthermore, the caudal fin vascularization assay in Tg(fli1:eGFP) Casper fish could be a promising preclinical model for testing the effects of different diets on angiogenesis and endothelial dysfunction.Item Open Access Integromic analysis of genetic variation and gene expression identifies networks for cardiovascular disease phenotypes(Lippincott Williams & Wilkins, 2015) Yao, C.; Chen, B. H.; Joehanes, R.; Otlu, B.; Zhang X.; Liu, C.; Huan, T.; Tastan, O.; Cupples, L. A.; Meigs, J. B.; Fox, C. S.; Freedman, J. E.; Courchesne, P.; O'Donnell, C. J.; Munson, P. J.; Keles, S.; Levy, D.BACKGROUND - : Cardiovascular disease (CVD) reflects a highly coordinated complex of traits. Although genome-wide association studies have reported numerous single nucleotide polymorphisms (SNPs) to be associated with CVD, the role of most of these variants in disease processes remains unknown. METHODS AND RESULTS - : We built a CVD network using 1512 SNPs associated with 21 CVD traits in genome-wide association studies (at P≤5×10) and cross-linked different traits by virtue of their shared SNP associations. We then explored whole blood gene expression in relation to these SNPs in 5257 participants in the Framingham Heart Study. At a false discovery rate <0.05, we identified 370 cis-expression quantitative trait loci (eQTLs; SNPs associated with altered expression of nearby genes) and 44 trans-eQTLs (SNPs associated with altered expression of remote genes). The eQTL network revealed 13 CVD-related modules. Searching for association of eQTL genes with CVD risk factors (lipids, blood pressure, fasting blood glucose, and body mass index) in the same individuals, we found examples in which the expression of eQTL genes was significantly associated with these CVD phenotypes. In addition, mediation tests suggested that a subset of SNPs previously associated with CVD phenotypes in genome-wide association studies may exert their function by altering expression of eQTL genes (eg, LDLR and PCSK7), which in turn may promote interindividual variation in phenotypes. CONCLUSIONS - : Using a network approach to analyze CVD traits, we identified complex networks of SNP-phenotype and SNP-transcript connections. Integrating the CVD network with phenotypic data, we identified biological pathways that may provide insights into potential drug targets for treatment or prevention of CVD.Item Open Access Non-covalent functionalized SWNTs as delivery agents for novel Bodipy-based potential PDT sensitizers(2009) Erbas, S.; Gorgulu, A.; Kocakusakogullari, M.; Akkaya, E. U.Pyrenyl-functionalized distyryl-Bodipy sensitizer attached non-covalently to SWNTs was shown to generate singlet oxygen when excited at 660 nm with a red LED array; this work emphasizes the potential of SWNT as a viable alternative carrier of bioactive agents, including photodynamic therapy sensitizers. © 2009 The Royal Society of Chemistry.