Circulatory and Respiratory Physiology Commons^™

Identification Of Proteins With Immune Stimulatory Activities From The Culture Filtrates Of Nontuberculous Mycobacteria, Christian Albert Agyei Acheampong

Biotechnology Theses

Nontuberculous mycobacteria (NTM) are the mycobacterial species other than Mycobacterium tuberculosis, which causes tuberculosis, and Mycobacterium leprae, which causes leprosy. Diseases caused by NTM are on the rise in the United States and are steadily becoming a significant public health problem globally, particularly in developed countries. Despite the ability of NTM pathogens to interact with the host immune system, the proteins responsible for eliciting host immune responses remain unidentified, making the accurate and timely diagnosis of the disease a challenge. In this study, we tested the hypothesis that NTM strains secrete proteins that stimulate immune responses. Our study …

Macrophage Angiotensin-Converting Enzyme Reduces Atherosclerosis By Increasing Peroxisome Proliferator-Activated Receptor Α And Fundamentally Changing Lipid Metabolism, Duoyao Cao, Zakir Khan, Xiaomo Li, Suguru Saito, Ellen A. Bernstein, Aaron R. Victor, Faizan Ahmed, Aoi O. Hoshi, Luciana C. Veiras, Tomohiro Shibata, Mingtian Che, Lei Cai, Michifumi Yamashita, Ryan E. Temel, Jorge F. Giani, Daniel J. Luthringer, Ajit S. Divakaruni, Derick Okwan-Duodu, Kenneth E. Bernstein

Saha Cardiovascular Research Center Faculty Publications

Aims The metabolic failure of macrophages to adequately process lipid is central to the aetiology of atherosclerosis. Here, we examine the role of macrophage angiotensin-converting enzyme (ACE) in a mouse model of PCSK9-induced atherosclerosis.

Methods and results Atherosclerosis in mice was induced with AAV-PCSK9 and a high-fat diet. Animals with increased macrophage ACE (ACE 10/10 mice) have a marked reduction in atherosclerosis vs. WT mice. Macrophages from both the aorta and peritoneum of ACE 10/10 express increased PPARα and have a profoundly altered phenotype to process lipids characterized by higher levels of the surface scavenger receptor CD36, increased uptake of …

Endogenous Mechanisms Regulating Myeloid Cell Mediated Inflammation During Acute Lung Injuries, Nathaniel Berg

Dissertations and Theses (Open Access)

Acute lung injuries (ALI) can result from both direct insults (e.g. pneumonia or inhalation injury), or systemic conditions such as sepsis or trauma. Current treatment options for patients are limited to supportive care and novel approaches are urgently needed. Appreciating the role of excessive inflammation that underlies the pathophysiology of ALI, we sought to identify endogenous mechanisms that dampen inflammation. Here we investigated two pathways that worked to limit excessive pulmonary inflammation in myeloid cells using a mouse model of sepsis-associated ALI. In the first approach we screened for microRNAs during the recovery phase of ALI that could potentially regulate …

Proteomic Alterations Of Hdl In Youth With Type 1 Diabetes And Their Associations With Glycemic Control: A Case-Control Study, Evgenia Gourgari, Junfeng Ma, Martin P. Playford, Nehal N. Mehta, Radoslav Goldman, Alan T. Remaley, Scott M. Gordon

Saha Cardiovascular Research Center Faculty Publications

Background: Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition.

Methods: This was a cross-sectional case–control study. Blood samples were obtained from patients with T1DM and …

Bisphenol A Increases Atherosclerosis In Pregnane X Receptor-Humanized Apoe Deficient Mice, Yipeng Sui, Se-Hyung Park, Robert N. Helsley, Manjula Sunkara, Frank J. Gonzalez, Andrew J. Morris, Changcheng Zhou

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA has recently been associated with increased risk of cardiovascular disease (CVD) in multiple large-scale human population studies, but the underlying mechanisms remain elusive. We previously reported that BPA activates the pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism and has pro-atherogenic effects in animal models upon activation. Interestingly, BPA is a potent agonist of human PXR but does not activate mouse or rat PXR signaling, which confounds the use of rodent models to evaluate mechanisms of BPA-mediated CVD risk. …

Renin Inhibition Reduces Hypercholesterolemia-Induced Atherosclerosis In Mice, Hong Lu, Debra L. Rateri, David L. Feldman, Richard Charnigo, Akiyoshi Fukamizu, Junji Ishida, Elizabeth Grace Oesterling, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

The role of the renin angiotensin system (RAS) in atherosclerosis is complex because of the involvement of multiple peptides and receptors. Renin is the rate-limiting enzyme in the production of all angiotensin peptides. To determine the effects of renin inhibition on atherosclerosis, we administered the novel renin inhibitor aliskiren over a broad dose range to fat-fed LDL receptor-deficient (Ldlr^-/-) mice. Renin inhibition resulted in striking reductions of atherosclerotic lesion size in both the aortic arch and the root. Subsequent studies demonstrated that cultured macrophages expressed all components of the RAS. To determine the role of macrophage-derived angiotensin in …