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Full-Text Articles in Life Sciences
Characterizing The Transcriptome Of Sirt6-Deficient Aortic Smooth Muscle Cells, Ryan J. Wong
Characterizing The Transcriptome Of Sirt6-Deficient Aortic Smooth Muscle Cells, Ryan J. Wong
Electronic Thesis and Dissertation Repository
Several vascular diseases are marked by dysfunctional vascular smooth muscle cells (VSMCs). Our group has found that the knockout of the NAD+-dependent histone deacetylase sirtuin 6 (Sirt6), specifically in VSMCs, increases oxidative stress-induced DNA damage, inflammation, and aortic aneurysms in mice. To study the molecular mechanisms that drive VSMC dysfunction in Sirt6-deficiency, I established a primary culture model of Sirt6 deletion in VSMCs with Cre-lox technology. Through RNA sequencing of Sirt6-deficient VSMCs, we have identified modest but coordinated upregulations in transcripts involved in nucleosome assembly, inflammation, cell death, and autoimmunity. Immunostaining in histological sections of VSMC-specific …
Monocyte Mri Relaxation Rates Are Regulated By Extracellular Iron And Hepcidin, Praveen S.B Dassanayake
Monocyte Mri Relaxation Rates Are Regulated By Extracellular Iron And Hepcidin, Praveen S.B Dassanayake
Electronic Thesis and Dissertation Repository
Monocytes are an important immune cell type in chronic inflammatory conditions like atherosclerosis and heart failure. The increase in number of monocytes released to the peripheral blood circulation, the differentiation of monocytes to macrophages, and the presence of different macrophage subpopulations during pro- and anti-inflammatory stages of tissue injury may provide markers for monitoring inflammation. In particular, changes in monocyte iron metabolism during an inflammatory response may increase the possibility of tracking these immune cells non-invasively using magnetic resonance imaging (MRI). When secretion of the polypeptide hormone hepcidin is stimulated during inflammation, it binds the iron export protein ferroportin (FPN) …
The Role Of Sirtuin 6 In Maintaining Vascular Integrity, Sharon Z. Leung
The Role Of Sirtuin 6 In Maintaining Vascular Integrity, Sharon Z. Leung
Electronic Thesis and Dissertation Repository
Oxidative stress is an underlying cause for vascular pathologies including inflammation, hypertension, and atherosclerosis. Sirtuins (SIRTs) are a family of NAD+ dependent deacetylases with pronounced roles in cellular metabolism and aging. SIRT6 is expressed in vascular smooth muscle cells (SMCs) and may offer protection from oxidative stress-induced damage. To study the role of SIRT6 in SMCs, we created a novel strain of SMC-specific SIRT6-deficient (SIRT6KO) mice with Cre-lox technology. Because no defects were observed in the aortas of SIRT6KO mice, they were then infused with angiotensin II (Ang II) to induce oxidative stress. Compared with vehicle controls, SIRT6KO mice developed …
Regulation Of Lipid Homeostasis, Inflammatory Signalling And Atherosclerosis By The Peroxisome Proliferator-Activated Receptor Delta, Lazar A. Bojic
Regulation Of Lipid Homeostasis, Inflammatory Signalling And Atherosclerosis By The Peroxisome Proliferator-Activated Receptor Delta, Lazar A. Bojic
Electronic Thesis and Dissertation Repository
The peroxisome proliferator-activated receptor (PPAR) δ is a ligand-dependent transcription factor that has been implicated in metabolic and inflammatory regulation. The molecular and physiological mechanisms by which PPARδ activation regulates lipid metabolism, inflammatory signaling and protection from atherosclerosis in states of metabolic disturbance such as insulin resistance and dyslipidemia, were investigated in a series of in vitro and in vivo studies. In vitro experiments demonstrated that PPARδ activation inhibits atherogenic lipoprotein-induced lipid accumulation and the associated proinflammatory responses. The primary mechanisms for these effects were increased fatty acid β-oxidation, decreased lipoprotein lipase (LPL) activity, reduced MAPK signaling and improved insulin …