Medicine and Health Sciences Commons^™

Cerebrovascular Pathology In Down Syndrome And Alzheimer Disease, Elizabeth Head, Michael J. Phelan, Eric Doran, Ronald C. Kim, Wayne W. Poon, Frederick A. Schmitt, Ira T. Lott

Sanders-Brown Center on Aging Faculty Publications

People with Down syndrome (DS) are at high risk for developing Alzheimer disease (AD) with age. Typically, by age 40 years, most people with DS have sufficient neuropathology for an AD diagnosis. Interestingly, atherosclerosis and hypertension are atypical in DS with age, suggesting the lack of these vascular risk factors may be associated with reduced cerebrovascular pathology. However, because the extra copy of APP leads to increased beta-amyloid peptide (Aβ) accumulation in DS, we hypothesized that there would be more extensive and widespread cerebral amyloid angiopathy (CAA) with age in DS relative to sporadic AD. To test this hypothesis CAA, …

Trak2, A Novel Regulator Of Abca1 Expression, Cholesterol Efflux And Hdl Biogenesis, Nicole J. Lake, Rachael L. Taylor, Hugh Trahair, K. N. Harikrishnan, Joanne E. Curran, Marcio Almeida, Hemant Kulkarni, Matthew P. Johnson, Thomas D. Dyer, Michael Mahaney, Harald H. H. Goring, John Blangero

School of Medicine Publications and Presentations

Aims: The recent failures of HDL-raising therapies have underscored our incomplete understanding of HDL biology. Therefore there is an urgent need to comprehensively investigate HDL metabolism to enable the development of effective HDL-centric therapies. To identify novel regulators of HDL metabolism, we performed a joint analysis of human genetic, transcriptomic, and plasma HDL-cholesterol (HDL-C) concentration data and identified a novel association between trafficking protein, kinesin binding 2 (TRAK2) and HDL-C concentration. Here we characterize the molecular basis of the novel association between TRAK2 and HDL-cholesterol concentration.

Methods and results: Analysis of lymphocyte transcriptomic data together with plasma HDL from the …

Cruciferous And Allium Vegetable Intakes Are Inversely Associated With 15‐Year Atherosclerotic Vascular Disease Deaths In Older Adult Women, Lauren Blekkenhorst, Catherine P. Bondonno, Joshua Lewis, Amanda Devine, Kun Zhu, Wai Lim, Richard Woodman, Lawrence Beilin, Richard Prince, Jonathan M. Hodgson

Research outputs 2014 to 2021

Background

Higher vegetable intake is consistently associated with lower atherosclerotic vascular disease (ASVD) events. However, the components responsible and mechanisms involved are uncertain. Nonnutritive phytochemicals may be involved. The objective of this study was to investigate the associations of total vegetable intake and types of vegetables grouped according to phytochemical constituents with ASVD mortality.

Methods and Results

The cohort consisted of 1226 Australian women aged 70 years and older without clinical ASVD or diabetes mellitus at baseline (1998). Vegetable intakes were calculated per serving (75 g/d) and were also classified into prespecified types relating to phytochemical constituents. ASVD‐related deaths were …

Targeting Hepatic Heparin-Binding Egf-Like Growth Factor (Hb-Egf) Induces Anti-Hyperlipidemia Leading To Reduction Of Angiotensin Ii-Induced Aneurysm Development, Seonwook Kim, Lihua Yang, Seongu Kim, Richard G. Lee, Mark J. Graham, Judith A. Berliner, Aldons J. Lusis, Lei Cai, Ryan E. Temel, Debra L. Rateri, Sangderk Lee

Saha Cardiovascular Research Center Faculty Publications

Objective

The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model.

Approach and results

Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin …

Genetic Associations With Lipoprotein Subfraction Measures Differ By Ethnicity In The Multi-Ethnic Study Of Atherosclerosis (Mesa), Zhe Wang, Ani Manichukal, David C. Goff, Samia Mora, Jose M. Ordovas, Nicholas M. Pajewski, Wendy S. Post, Jerome I. Rotter, Michele M. Sale, Stephanie A. Santorico, David Siscovick, Michael Y. Tsai, Donna K. Arnett, Stephen Rich, Alexis C. Frazier-Wood

Epidemiology and Environmental Health Faculty Publications

A recent genome-wide association study associated 62 single nucleotide polymorphisms (SNPs) from 43 genomic loci, with fasting lipoprotein subfractions in European–Americans (EAs) at genome-wide levels of significance across three independent samples. Whether these associations are consistent across ethnicities with a non-European ancestry is unknown. We analyzed 15 lipoprotein subfraction measures, on 1677 African–Americans (AAs), 1450 Hispanic–Americans (HAs), and 775 Chinese–Americans (CHN) participating in the multi-ethnic study of atherosclerosis (MESA). Genome-wide data were obtained using the Affymetrix 6.0 and Illumina HumanOmni chips. Linear regression models between genetic variables and lipoprotein subfractions were adjusted for age, gender, body mass index, smoking, study …

Exploring Adenosine Receptor Ligands: Potential Role In The Treatment Of Cardiovascular Diseases, Werner J. Geldenhuys, Ahmad Hanif, June Yun, Mohammed A. Nayeem

Clinical and Translational Science Institute

Cardiovascular diseases remain the number one diseases affecting patients’ morbidity and mortality. The adenosine receptors are G-protein coupled receptors which have been of interest for drugs target for the treatment of multiple diseases ranging from cardiovascular to neurological. Adenosine receptors have been connected to several biological pathways affecting the physiology and pathology of the cardiovascular system. In this review, we will cover the different adenosine receptor ligands that have been identified to interact with adenosine receptors and affect the vascular system. These ligands will be evaluated from clinical as well as medicinal chemistry perspectives with more emphasis on how structural …

Genome- And Cd4+ T-Cell Methylome-Wide Association Study Of Circulating Trimethylamine-N-Oxide In The Genetics Of Lipid Lowering Drugs And Diet Network (Goldn), Stella Aslibekyan, Marguerite R. Irvin, Bertha A. Hidalgo, Rodney T. Perry, Elias J. Jeyarajah, Erwin Garcia, Irina Shalaurova, Paul N. Hopkins, Michael A. Province, Hemant K. Tiwari, Jose M. Ordovas, Devin M. Absher, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Trimethylamine-N-oxide (TMAO), an atherogenic metabolite species, has emerged as a possible new risk factor for cardiovascular disease. Animal studies have shown that circulating TMAO levels are regulated by genetic and environmental factors. However, large-scale human studies have failed to replicate the observed genetic associations, and epigenetic factors such as DNA methylation have never been examined in relation to TMAO levels.

Methods and results: We used data from the family-based Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) to investigate the heritable determinants of plasma TMAO in humans. TMAO was not associated with other plasma markers of cardiovascular disease, …

Population-Based Cohort Study In Outcome Of Phased Progression Of Atherosclerosis In China (Persuade): Objective, Rationale And Design, Dong-Kai Shan, Yong Zhou, You-Xin Wang, Xiang Gao, Wei Wang, Jun-Jie Yang, Yun-Dai Chen

Research outputs 2014 to 2021

The coronary artery calcification score and pericardial fat volume have recently been reported to be strongly associated with the severity and presence of coronary atherosclerosis. However, no studies have explored the outcome of phased progression of atherosclerosis by non-contrast computed tomography in asymptomatic people in China. The population-based cohort study in outcome of phased progression of atherosclerosis in China (PERSUADE), an observational, longitudinal and prospective cohort study in a target population of healthy subjects based in Jidong Oilfield (China), prospectively analyzes the outcome of phased progression of atherosclerosis by non-contrast computed tomography in healthy population. The results of this study …

Myeloperoxidase-Mediated Protein Lysine Oxidation Generates 2- Aminoadipic Acid And Lysine Nitrile In Vivo, Hongqiao Lin, Bruce S. Levison, Jennifer A. Buffa, Ying Huang, Xiaoming Fu, Zeneng Wang, Valentin Gogonea, Joseph A. Didonato, Stanley L. Hazen

Chemistry Faculty Publications

Recent studies reveal 2-aminoadipic acid (2-AAA) is both elevated in subjects at risk for diabetes and mechanistically linked to glucose homeostasis. Prior studies also suggest enrichment of protein-bound 2-AAA as an oxidative post-translational modification of lysyl residues in tissues associated with degenerative diseases of aging. While in vitro studies suggest redox active transition metals or myeloperoxidase (MPO) generated hypochlorous acid (HOCl) may produce protein-bound 2-AAA, the mechanism(s) responsible for generation of 2- AAA during inflammatory diseases are unknown. In initial studies we observed that traditional acid- or basecatalyzed protein hydrolysis methods previously employed to measure tissue 2-AAA can artificially generate …

Cigarette Smoking And Cardio-Renal Events In Patients With Atherosclerotic Renal Artery Stenosis., Christopher A Drummond, Pamela S Brewster, Wencan He, Kaili Ren, Yanmei Xie, Katherine Tuttle, Steven T Haller, Kenneth Jamerson, Lance D Dworkin, Donald E Cutlip, Timothy P Murphy, Ralph B D'Agostino, William L Henrich, Jiang Tian, Joseph I Shapiro, Christopher J Cooper

Articles, Abstracts, and Reports

Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731) clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population. Baseline data showed that smokers (n = 277 out of 931) were significantly younger at enrollment than non-smokers (63.3±9.1 years vs 72.4±7.8 years; p