Digital Commons Network^™

Infusion Of Reconstituted High-Density Lipoprotein, Csl112, In Patients With Atherosclerosis: Safety And Pharmacokinetic Results From A Phase 2a Randomized Clinical Trial, Pierluigi Tricoci, Denise M. D'Andrea, Paul A. Gurbel, Zhenling Yao, Marina Cuchel, Brion Winston, Robert Schott, Robert Weiss, Michael A. Blazing, Louis Cannon, Alison L. Bailey, Dominick J. Angiolillo, Andreas Gille, Charles L. Shear, Samuel D. Wright, John H. Alexander

Gill Heart & Vascular Institute Faculty Publications

Background CSL112 is a new formulation of human apolipoprotein A‐I (apoA‐I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double‐blind, multicenter, dose‐ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable atherosclerotic disease.

Methods and Results Patients were randomized to single ascending doses of CSL112 (1.7, 3.4, or 6.8 g) or placebo, administered over a 2‐hour period. Primary safety assessments consisted of alanine aminotransferase or aspartate aminotransferase elevations >3× upper limits of normal and study drug–related adverse events. Pharmacokinetic/pharmacodynamic assessments included apoA‐I plasma …

The Sea Lamprey Meiotic Map Improves Resolution Of Ancient Vertebrate Genome Duplications, Jeramiah James Smith, Melissa C. Keinath

Biology Faculty Publications

It is generally accepted that many genes present in vertebrate genomes owe their origin to two whole-genome duplications that occurred deep in the ancestry of the vertebrate lineage. However, details regarding the timing and outcome of these duplications are not well resolved. We present high-density meiotic and comparative genomic maps for the sea lamprey (Petromyzon marinus), a representative of an ancient lineage that diverged from all other vertebrates ~550 million years ago. Linkage analyses yielded a total of 95 linkage groups, similar to the estimated number of germline chromosomes (1n ~ 99), spanning a total of 5570.25 cM. …

Intracellular Listeria Monocytogenes Comprises A Minimal But Vital Fraction Of The Intestinal Burden Following Foodborne Infection, Grant S. Jones, Kate M. Bussell, Tanya Myers-Morales, Abigail M. Fieldhouse, Elsa N. Bou Ghanem, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Listeria monocytogenes is a highly adaptive bacterium that replicates as a free-living saprophyte in the environment as well as a facultative intracellular pathogen that causes invasive foodborne infections. The intracellular life cycle of L. monocytogenes is considered to be its primary virulence determinant during mammalian infection; however, the proportion of L. monocytogenes that is intracellular in vivo has not been studied extensively. In this report, we demonstrate that the majority of wild-type (strain EGDe) and mouse-adapted (InlA^m-expressing) L. monocytogenes recovered from the mesenteric lymph nodes (MLN) was extracellular within the first few days after foodborne infection. In addition, …

Amphiphilic Tobramycin Analogues As Antibacterial And Antifungal Agents, Sanjib K. Shrestha, Marina Y. Fosso, Keith D. Green, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

In this study, we investigated the in vitro antifungal activities, cytotoxicities, and membrane-disruptive actions of amphiphilic tobramycin (TOB) analogues. The antifungal activities were established by determination of MIC values and in time-kill studies. Cytotoxicity was evaluated in mammalian cell lines. The fungal membrane-disruptive action of these analogues was studied by using the membrane-impermeable dye propidium iodide. TOB analogues bearing a linear alkyl chain at their 6″-position in a thioether linkage exhibited chain length-dependent antifungal activities. Analogues with C₁₂ and C₁₄ chains showed promising antifungal activities against tested fungal strains, with MIC values ranging from 1.95 to 62.5 mg/liter …

Noncontact Diffuse Correlation Tomography Of Human Breast Tumor, Lian He, Yu Lin, Chong Huang, Daniel Irwin, Margaret M. Szabunio, Guoqiang Yu

Biomedical Engineering Faculty Publications

Our first step to adapt our recently developed noncontact diffuse correlation tomography (ncDCT) system for three-dimensional (3-D) imaging of blood flow distribution in human breast tumors is reported. A commercial 3-D camera was used to obtain breast surface geometry, which was then converted to a solid volume mesh. An ncDCT probe scanned over a region of interest on the mesh surface and the measured boundary data were combined with a finite element framework for 3-D image reconstruction of blood flow distribution. This technique was tested in computer simulations and in vivo human breasts with low-grade carcinoma. Results from computer simulations …

Pharmacodynamic Assays To Facilitate Preclinical And Clinical Development Of Pre-Mrna Splicing Modulatory Drug Candidates, Yihui Shi, Amanda S. Joyner, William Shadrick, Gustavo Palacios, Chandraiah Lagisetti, Philip M. Potter, Lidia C. Sambucetti, Stefan Stamm, Thomas R. Webb

Molecular and Cellular Biochemistry Faculty Publications

The spliceosome has recently emerged as a new target for cancer chemotherapy and novel antitumor spliceosome targeted agents are under development. Here, we describe two types of novel pharmacodynamic assays that facilitate drug discovery and development of this intriguing class of innovative therapeutics; the first assay is useful for preclinical optimization of small-molecule agents that target the SF3B1 spliceosomal protein in animals, the second assay is an ex vivo validated, gel-based assay for the measurement of drug exposure in human leukocytes. The first assay utilizes a highly specific bioluminescent splicing reporter, based on the skipping of exons 4-11 of a …

Engineering Plant Biomass Lignin Content And Composition For Biofuels And Bioproducts, Cassie Marie Welker, Vimal Kumar Balasubramanian, Carloalberto Petti, Krishan Mohan Rai, Seth Debolt, Venugopal Mendu

Horticulture Faculty Publications

Lignin is an aromatic biopolymer involved in providing structural support to plant cell walls. Compared to the other cell wall polymers, i.e., cellulose and hemicelluloses, lignin has been considered a hindrance in cellulosic bioethanol production due to the complexity involved in its separation from other polymers of various biomass feedstocks. Nevertheless, lignin is a potential source of valuable aromatic chemical compounds and upgradable building blocks. Though the biosynthetic pathway of lignin has been elucidated in great detail, the random nature of the polymerization (free radical coupling) process poses challenges for its depolymerization into valuable bioproducts. The absence of specific …

Benthic Collector And Grazer Communities Are Threatened By Hemlock Woolly Adelgid-Induced Eastern Hemlock Loss, Joshua K. Adkins, Lynne K. Rieske

Entomology Faculty Publications

Eastern hemlock (Tsuga canadensis (L.) is a foundation species in eastern North America where it is under threat from the highly invasive, exotic hemlock woolly adelgid (Adelges tsugae). Eastern hemlock is especially important in riparian areas of Central and Southern Appalachia, so we compared the spatial and temporal composition of benthic collector-gatherers, collector-filterers, and grazers in headwater streams with hemlock-dominated riparian vegetation to those with deciduous tree-dominated riparian vegetation to evaluate the extent to which adelgid-induced hemlock loss could influence composition and abundance of these two functional feeding groups. We found differences in benthic invertebrate abundance and …

Reversal Of Aging-Related Neuronal Ca2+ Dysregulation And Cognitive Impairment By Delivery Of A Transgene Encoding Fk506-Binding Protein 12.6/1b To The Hippocampus, John C. Gant, Kuey-Chu Chen, Inga Kadish, Eric M. Blalock, Olivier Thibault, Nada M. Porter, Philip W. Landfield

Pharmacology and Nutritional Sciences Faculty Publications

Brain Ca(2+) regulatory processes are altered during aging, disrupting neuronal, and cognitive functions. In hippocampal pyramidal neurons, the Ca(2+)-dependent slow afterhyperpolarization (sAHP) exhibits an increase with aging, which correlates with memory impairment. The increased sAHP results from elevated L-type Ca(2+) channel activity and ryanodine receptor (RyR)-mediated Ca(2+) release, but underlying molecular mechanisms are poorly understood. Previously, we found that expression of the gene encoding FK506-binding protein 12.6/1b (FKBP1b), a small immunophilin that stabilizes RyR-mediated Ca(2+) release in cardiomyocytes, declines in hippocampus of aged rats and Alzheimer's disease subjects. Additionally, knockdown/disruption of hippocampal FKBP1b in young rats augments neuronal Ca(2+) responses. …

A Quantitative Perspective On Surface Marker Selection For The Isolation Of Functional Tumor Cells, Calvin F. Cahall, Jacob L. Lilly, Edward A. Hirschowitz, Brad J. Berron

Chemical and Materials Engineering Faculty Publications

Much effort has gone into developing fluid biopsies of patient peripheral blood for the monitoring of metastatic cancers. One common approach is to isolate and analyze tumor cells in the peripheral blood. Widespread clinical implementation of this approach has been hindered by the current choice of targeting epithelial markers known to be highly variable in primary tumor sites. Here, we review current antigen-based tumor cell isolation strategies and offer biological context for commonly studied cancer surface markers. Expression levels of the most common markers are quantitated for three breast cancer and two non-small cell lung cancer (NSCLC) lineage models. These …

The Mitochondrial Peptidase Pitrilysin Degrades Islet Amyloid Polypeptide In Beta-Cells, Hanjun Guan, K. Martin Chow, Eunsuk Song, Nirmal Verma, Florin Despa, Louis B. Hersh

Molecular and Cellular Biochemistry Faculty Publications

Amyloid formation and mitochondrial dysfunction are characteristics of type 2 diabetes. The major peptide constituent of the amyloid deposits in type 2 diabetes is islet amyloid polypeptide (IAPP). In this study, we found that pitrilysin, a zinc metallopeptidase of the inverzincin family, degrades monomeric, but not oligomeric, islet amyloid polypeptide in vitro. In insulinoma cells when pitrilysin expression was decreased to 5% of normal levels, there was a 60% increase in islet amyloid polypeptide-induced apoptosis. In contrast, overexpression of pitrilysin protects insulinoma cells from human islet amyloid polypeptide-induced apoptosis. Since pitrilysin is a mitochondrial protein, we used immunofluorescence staining …

Eldred & The New Rationality, Brian L. Frye

Law Faculty Scholarly Articles

Historically, the rational basis test has been a constitutional rubber stamp. In Eldred v. Ashcroft and Golan v. Holder, the Supreme Court applied the rational basis test and respectively held that Congress could extend the copyright term of existing works and restore copyright protection of public domain works, despite evidence that Congress intended to benefit copyright owners at the expense of the public. But in Lawrence v. Texas and United States v. Windsor, the Supreme Court seems to have applied the rational basis test and held that state and federal laws were unconstitutional because they were motivated by …

Plant Species' Origin Predicts Dominance And Response To Nutrient Enrichment And Herbivores In Global Grasslands, Eric W. Seabloom, Elizabeth T. Borer, Yvonne M. Buckley, Elsa E. Cleland, Kendi F. Davies, Jennifer Firn, W. Stanley Harpole, Yann Hautier, Eric M. Lind, Andrew S. Macdougall, John L. Orrock, Suzanne M. Prober, Peter B. Adler, T. Michael Anderson, Jonathan D. Bakker, Lori A. Biederman, Dana M. Blumenthal, Cynthia S. Brown, Lars A. Brudvig, Marc Cadotte, Chengjin Chu, Kathryn L. Cottingham, Michael J. Crawley, Ellen I. Damschen, Carla M. Dantonio, Nicole M. Decrappeo, Guozhen Du, Philip A. Fay, Paul Frater, Daniel S. Gruner, Nicole Hagenah, Andy Hector, Helmut Hillebrand, Kirsten S. Hofmockel, Hope C. Humphries, Virginia L. Jin, Adam Kay, Kevin P. Kirkman, Julia A. Klein, Johannes M. H. Knops, Kimberly J. La Pierre, Laura Ladwig, John G. Lambrinos, Qi Li, Wei Li, Robin Marushia, Rebecca L. Mcculley, Brett A. Melbourne, Charles E. Mitchell, Joslin L. Moore, John Morgan, Brent Mortensen, Lydia R. O'Halloran, David A. Pyke, Anita C. Risch, Mahesh Sankaran, Martin Schuetz, Anna Simonsen, Melinda D. Smith, Carly J. Stevens, Lauren Sullivan, Elizabeth Wolkovich, Peter D. Wragg, Justin Wright, Louie Yang

Plant and Soil Sciences Faculty Publications

Exotic species dominate many communities; however the functional significance of species' biogeographic origin remains highly contentious. This debate is fuelled in part by the lack of globally replicated, systematic data assessing the relationship between species provenance, function and response to perturbations. We examined the abundance of native and exotic plant species at 64 grasslands in 13 countries, and at a subset of the sites we experimentally tested native and exotic species responses to two fundamental drivers of invasion, mineral nutrient supplies and vertebrate herbivory. Exotic species are six times more likely to dominate communities than native species. Furthermore, while experimental …

Zbtb20 Is A Sequence-Specific Transcriptional Repressor Of Alpha-Fetoprotein Gene, Hai Zhang, Dongmei Cao, Luting Zhou, Ye Zhang, Xiaoqin Guo, Hui Li, Yuxia Chen, Brett T. Spear, Jia-Wei Wu, Zhifang Xie, Weiping J Zhang

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Alpha-fetoprotein (AFP) represents a classical model system to study developmental gene regulation in mammalian cells. We previously reported that liver ZBTB20 is developmentally regulated and plays a central role in AFP postnatal repression. Here we show that ZBTB20 is a sequence-specific transcriptional repressor of AFP. By ELISA-based DNA-protein binding assay and conventional gel shift assay, we successfully identified a ZBTB20-binding site at -104/-86 of mouse AFP gene, flanked by two HNF1 sites and two C/EBP sites in the proximal promoter. Importantly, mutation of the core sequence in this site fully abolished its binding to ZBTB20 in vitro, as well …

B Lymphocytes Are Required During The Early Priming Of Cd4+ T Cells For Clearance Of Pneumocystis Infection In Mice, Michael M. Opata, Melissa L. Hollifield, Frances E. Lund, Troy D. Randall, Robert Dunn, Beth A. Garvy, David J. Feola

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B cells play a critical role in the clearance of Pneumocystis. In addition to production of Pneumocystis-specific Abs, B cells are required during the priming phase for CD4⁺ T cells to expand normally and generate memory. Clearance of Pneumocystis was found to be dependent on Ag specific B cells and on the ability of B cells to secrete Pneumocystis-specific Ab, as mice with B cells defective in these functions or with a restricted BCR were unable to control Pneumocystis infection. Because Pneumocystis-specific antiserum was only able to partially protect B cell–deficient mice from infection, we …

Full-Range Public Health Leadership, Part 2: Qualitative Analysis And Synthesis, Erik L. Carlton, James W. Holsinger Jr., Martha C. Riddell, Heather Bush

Preventive Medicine and Environmental Health Faculty Publications

Public health leadership is an important topic in the era of U.S. health reform, population health innovation, and health system transformation. This study utilized the full-range leadership model in order to examine the public health leadership. We sought to understand local public health leadership from the perspective of local health department leaders and those who work with and for them. Public health leadership was explored through interviews and focus groups with directors (n = 4) and staff (n = 33) from local health departments. Qualitative analytic methods included reflexive journals, code-recode procedures, and member checking, with analysis facilitated …

Toll-Like Receptors And Dectin-1, A C-Type Lectin Receptor, Trigger Divergent Functions In Cns Macrophages, John C. Gensel, Yan Wang, Zhen Guan, Kyle A. Beckwith, Kaitlyn J. Braun, Ping Wei, Dana M. Mctigue, Phillip G. Popovich

Spinal Cord and Brain Injury Research Center Faculty Publications

Spinal cord injury (SCI) activates macrophages, endowing them with both reparative and pathological functions. The mechanisms responsible for these divergent functions are unknown but are likely controlled through stochastic activation of different macrophage receptor subtypes. Various danger-associated molecular patterns released from dying cells in the injured spinal cord likely activate distinct subtypes of macrophage pattern recognition receptors, including bacterial toll-like receptors (TLRs) and fungal C-type lectin receptors (e.g., dectin-1). To determine the in vivo consequences of activating these receptors, ligands specific for TLR2 or dectin-1 were microinjected, alone or in combination, into intact spinal cord. Both ligands elicit a florid …

Regression Of Gastric Cancer By Systemic Injection Of Rna Nanoparticles Carrying Both Ligand And Sirna, Daxiang Cui, Chunlei Zhang, Bing Liu, Yi Shu, Tong Du, Dan Shu, Kan Wang, Fangping Dai, Yanlei Liu, Chao Li, Fei Pan, Yuming Yang, Jian Ni, Hui Li, Beate Brand-Saberi, Peixuan Guo

Markey Cancer Center Faculty Publications

Gastric cancer is the second leading cause of cancer-related death worldwide. RNA nanotechnology has recently emerged as an important field due to recent finding of its high thermodynamic stability, favorable and distinctive in vivo attributes. Here we reported the use of the thermostable three-way junction (3WJ) of bacteriophage phi29 motor pRNA to escort folic acid, a fluorescent image marker and BRCAA1 siRNA for targeting, imaging, delivery, gene silencing and regression of gastric cancer in animal models. In vitro assay revealed that the RNA nanoparticles specifically bind to gastric cancer cells, and knock-down the BRCAA1 gene. Apoptosis of gastric cancer cells …

Mackenzie, Catriona; Rogers, Wendy; And Dodds, Susan, Eds. Vulnerability: New Essays In Ethics And Feminist Philosophy (Review), Anita Superson

Philosophy Faculty Publications

No abstract provided.

Can Dentistry Have Two Contracts With The Public?, David A. Nash

Oral Health Science Faculty Publications

The social contract is an implicit agreement between parts of society and society as a whole. Since the Middle Ages, the learned professions, recently including dentistry, have had a covenantal relationship with the public based on trust, exchanging monopoly privileges for benefiting the public good. Unlike commercial trade in commodities, professional relationships are grounded in ensuring an adequate level of oral health to all. A second contract is emerging where dentists relate to society as business operators, exchanging commodity services for a price. Recent actions by the Federal Trade Commission and the U.S. Supreme Court make it unlikely that dentistry …

All-Weather Surfaces For Cattle Watering Facilities, Stephen F. Higgins, Kylie Schmidt, Donald J. Stamper, Kevin Laurent

Agriculture and Natural Resources Publications

A livestock watering area includes a watering facility and the heavy-use-area (HUA) surrounding it. Without protection, the HUA can develop surface depressions. Surface depressions can render the watering facility inaccessible and no longer frost-proof. Surface depressions also collect rainwater and excrement, creating mud and conditions adverse to livestock health (Figure 1).

Slaframine Toxicosis Or “Slobbers” In Cattle And Horses, Michelle Arnold, S. Ray Smith

Agriculture and Natural Resources Publications

An exceptionally wet summer weather pattern favors the growth of fungi on plants in the field and increases the risk for production of mycotoxins. Mycotoxins are naturally occurring compounds, some of which are toxic to cattle and horses, produced by fungi invading plant material. In the late 1940s and through the 1950s, beef and dairy producers and horse owners reported outbreaks of excessive salivation (slobbering) in cattle and horses associated with the consumption of second-cutting red clover (Trifolium pratense) and occasionally other legumes in the form of hay, pasture, or silage. It was not until the 1960s that …

Acute Or Atypical Interstitial Pneumonia (Aip), Michelle Arnold, Jeff Lehmkuhler

Agriculture and Natural Resources Publications

Acute or atypical interstitial pneumonia (AIP) is terminology used by veterinary pathologists to describe a characteristic pattern of damage in the lungs of cattle. At necropsy, the first indication of AIP-affected lungs is they fill the thorax and do not collapse like normal lungs when the chest cavity is opened. On further investigation, the AIP lungs are found to be semi-firm with a rubbery texture; not hard and consolidated as occurs in bacterial bronchopneumonia. Large air bubbles are found between portions of the lung (see Figure 1, “interlobular” or “bullous” emphysema) and the cut surface of the lung may appear …

Staggers (Tremorgenic Syndrome), Michelle Arnold

Agriculture and Natural Resources Publications

“Staggers” is an all-inclusive term for a group of nervous system disorders caused by indole-diterpenoid mycotoxins produced by various types of fungi on forages. These mycotoxins are collectively known as “tremorgens” (Table 1), and they may be found in several types of grasses at varying stages of maturity. The three main grass types associated with tremorgenic syndrome are Paspalum spp. (dallisgrass and bahiagrass), Cynodon dactylon (bermudagrass) and Lolium perenne (perennial ryegrass). Clinical signs are characterized by tremors and incoordination that tend to worsen with excitement or movement.

Changes In Serum Strongylus Vulgaris-Specific Antibody Concentrations In Response To Anthelmintic Treatment Of Experimentally Infected Foals, Martin Krarup Nielsen, Jessica Scare, Holli Sullivan Gravatte, Jennifer Lynn Bellaw, Julio C. Prado, Craig Robert Reinemeyer

Maxwell H. Gluck Equine Research Center Faculty Publications

Strongylus vulgaris is the most pathogenic nematode parasite of horses. Its extensive migration in the mesenteric blood vessels can lead to life-threatening intestinal infarctions. Recent work has shown that this parasite is still identified among managed horse populations. A serum enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of migrating larvae of S. vulgaris. Previous work has documented an increase in ELISA values following larvicidal treatment with ivermectin and suggested that the target parasite antigen is primarily produced by the later larval stages. The aim of this study was to experimentally inoculate cohorts of foals with S. …

The Effects Of Antiepileptic Inducers In Neuropsychopharmacology, A Neglected Issue. Part Ii: Pharmacological Issues And Further Understanding, Jose De Leon

Psychiatry Faculty Publications

The literature on inducers in epilepsy and bipolar disorder is seriously contaminated by false negative findings. Part II of this comprehensive review on antiepileptic drug (AED) inducers provides clinicians with further educational material about the complexity of interpreting AED drug-drug interactions.

The basic pharmacology of induction is reviewed including the cytochrome P450 (CYP) isoenzymes, the Uridine Diphosphate Glucuronosyltransferases (UGTs), and P-glycoprotein (P-gp). CYP2B6 and CYP3A4 are very sensitive to induction. CYP1A2 is moderately sensitive while CYP2C9 and CYP2C19 are only mildly sensitive. CYP2D6 cannot be induced by medications. Induction of UGT and P-gp are poorly understood. The induction of metabolic …

A Genetic Porcine Model Of Cancer, Lawrence B. Schook, Tiago V. Collares, Wenping Hu, Ying Liang, Fernanda M. Rodrigues, Laurie A. Rund, Kyle M. Schachtschneider, Fabiana K. Seixas, Kuldeep Singh, Kevin D. Wells, Eric M. Walters, Randall S. Prather, Christopher M. Counter

Toxicology and Cancer Biology Faculty Publications

The large size of the pig and its similarity in anatomy, physiology, metabolism, and genetics to humans make it an ideal platform to develop a genetically defined, large animal model of cancer. To this end, we created a transgenic "oncopig" line encoding Cre recombinase inducible porcine transgenes encoding KRAS^G12D and TP^53R167H, which represent a commonly mutated oncogene and tumor suppressor in human cancers, respectively. Treatment of cells derived from these oncopigs with the adenovirus encoding Cre (AdCre) led to KRAS^G12D and TP^53R167H expression, which rendered the cells transformed in culture and tumorigenic when engrafted into …

Noncontact Diffuse Optical Assessment Of Blood Flow Changes In Head And Neck Free Tissue Transfer Flaps, Chong Huang, Yu Lin, Yu Shang, Guoqiang Yu, Jeffrey Radabaugh, Rony Aouad, Thomas J. Gal, Amit B. Patel, Joseph Valentino

Biomedical Engineering Faculty Publications

Knowledge of tissue blood flow (BF) changes after free tissue transfer may enable surgeons to predict the failure of flap thrombosis at an early stage. This study used our recently developed noncontact diffuse correlation spectroscopy to monitor dynamic BF changes in free flaps without getting in contact with the targeted tissue. Eight free flaps were elevated in patients with head and neck cancer; one of the flaps failed. Multiple BF measurements probing the transferred tissue were performed during and post the surgical operation. Postoperative BF values were normalized to the intraoperative baselines (assigning “1”) for the calculation of relative BF …

Keeping Up With New Legal Titles, Franklin L. Runge

Law Faculty Scholarly Articles

In this book review, Franklin L. Runge discusses In Food We Trust: The Politics of Purity in American Food Regulation by Courtney I. P. Thomas.

Serum Amyloid A Facilitates Early Lesion Development In Ldlr-/- Mice, Paulette A. Krishack, Clarissa V. Bhanvadia, John Lukens, Timothy J. Sontag, Maria C. De Beer, Godfrey S. Getz, Catherine A. Reardon

Physiology Faculty Publications

BACKGROUND: Atherosclerosis is a chronic inflammatory disorder, and several studies have demonstrated a positive association between plasma serum amyloid A (SAA) levels and cardiovascular disease risk. The aim of the study was to examine whether SAA has a role in atherogenesis, the underlying basis of most cardiovascular disease.

METHODS AND RESULTS: Mice globally deficient in acute-phase isoforms Saa1 and Saa2 (Saa^-/-) were crossed to Ldlr^-/- mice (Saa^-/-Ldlr^-/-). Saa^-/-Ldlr^-/- mice demonstrated a 31% reduction in lesional area in the ascending aorta but not in the aortic root or innominate …