Sirtuin 6 Protects Against Oxidative Stress and Vascular Dysfunction in Mice.

Sirtuin deacetylases are major regulators of organismal aging, and while depletion of sirtuin 6 (SIRT6) in mice results in a profound progeroid phenotype, the role of SIRT6 in the regulation of vasomotor function is unknown. Thus, our objective was to test the hypothesis that reductions in SIRT6 elicit endothelial dysfunction in young, genetically altered mice. We used young (3 month old), littermate-matched, SIRT6 wild-type (WT), and SIRT6 heterozygous (HET) mice.

Effects of Altering Mitochondrial Antioxidant Capacity on Molecular and Phenotypic Drivers of Fibrocalcific Aortic Valve Stenosis.

While a small number of studies suggest that oxidative stress has an influential role in fibrocalcific aortic valve disease (FCAVD), the roles of specific antioxidant enzymes in progression of this disease remain poorly understood. Here, we focused on selectively altering mitochondrial-derived oxidative stress-which has been shown to alter progression of a myriad of age-associated diseases-on the progression of molecular and phenotypic drivers of FCAVD. We generated low-density lipoprotein receptor-deficient, Apolipoprotein B100-only mice (LA) that were either haploinsufficient for MnSOD ( ) or genetically overexpressing MnSOD ( ).

MnSOD protects against vascular calcification independent of changes in vascular function in hypercholesterolemic mice.

Background And Aims: The overall goal of this study was to determine the effects of MnSOD-deficiency on vascular structure and function in hypercholesterolemic mice. Previous work suggested that increases in mitochondrial-derived reactive oxygen species (ROS) can exacerbate vascular dysfunction and atherosclerosis. It remains unknown, however, how MnSOD-deficiency and local compensatory mechanisms impact atherosclerotic plaque composition.

Nonbiased Molecular Screening Identifies Novel Molecular Regulators of Fibrogenic and Proliferative Signaling in Myxomatous Mitral Valve Disease.

Background: Pathological processes underlying myxomatous mitral valve degeneration (MMVD) remain poorly understood. We sought to identify novel mechanisms contributing to the development of this condition.

Methods And Results: Microarrays were used to measure gene expression in 11 myxomatous and 11 nonmyxomatous human mitral valves.

Transcriptional and phenotypic changes in aorta and aortic valve with aging and MnSOD deficiency in mice.

The purpose of this study was to characterize changes in antioxidant and age-related gene expression in aorta and aortic valve with aging, and test the hypothesis that increased mitochondrial oxidative stress accelerates age-related endothelial and aortic valve dysfunction. Wild-type (MnSOD(+/+)) and manganese SOD heterozygous haploinsufficient (MnSOD(+/-)) mice were studied at 3 and 18 mo of age. In aorta from wild-type mice, antioxidant expression was preserved, although there were age-associated increases in Nox2 expression.

TGF-β signalling and reactive oxygen species drive fibrosis and matrix remodelling in myxomatous mitral valves.

Aims: Myxomatous mitral valve disease (MMVD) is associated with leaflet thickening, fibrosis, matrix remodelling, and leaflet prolapse. Molecular mechanisms contributing to MMVD, however, remain poorly understood. We tested the hypothesis that increased transforming growth factor-β (TGF-β) signalling and reactive oxygen species (ROS) are major contributors to pro-fibrotic gene expression in human and mouse mitral valves.

Original research in the classroom: why do zebrafish spawn in the morning?

As part of an upper level undergraduate developmental biology course at the University of Minnesota Duluth, we developed a unit in which students carried out original research as part of a cooperative class project. Students had the opportunity to gain experience in the scientific method from experimental design all of the way through to the preparation of publication on their research that included text, figures, and tables. This kind of inquiry-based learning has been shown to have many benefits for students, including increased long-term learning and a better understanding of the process of scientific discovery.

Sophorolipids and their derivatives are lethal against human pancreatic cancer cells.

Introduction: We have previously demonstrated that sophorolipids, a class of easily chemoenzymatically modifiable glycolipids, possess anti-inflammatory effects in vitro and in vivo. Since glycolipids have been shown to have anticancer activity, we investigated the effects of sophorolipids and their derivatives against pancreatic cancer.

Materials And Methods: Human pancreatic carcinoma cells were treated with increasing concentrations of sophorolipid natural mixture or select derivatives (ethyl ester, methyl ester, ethyl ester monoacetate, ethyl ester diacetate, acidic sophorolipid [AS], lactonic sophorolipid diacetate [LSD]) for 24 h and assessed for cell necrosis (cytotoxicity-lactate dehydrogenase release).