A5102992339- Atherosclerosis and Cardiovascular Diseases
- Lipoproteins and Cardiovascular Health
- Cholesterol and Lipid Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Coronary Interventions and Diagnostics
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Cerebrovascular and Carotid Artery Diseases
- Cardiac Imaging and Diagnostics
- Cancer, Lipids, and Metabolism
- Cell Adhesion Molecules Research
- Hormonal and reproductive studies
- Hormonal Regulation and Hypertension
- Digestive system and related health
- Histone Deacetylase Inhibitors Research
- Pancreatic function and diabetes
- Antiplatelet Therapy and Cardiovascular Diseases
- Amino Acid Enzymes and Metabolism
- Receptor Mechanisms and Signaling
- Cholinesterase and Neurodegenerative Diseases
- Aortic aneurysm repair treatments
- Chemokine receptors and signaling
- Lipid metabolism and disorders
- Bone and Dental Protein Studies
- Protease and Inhibitor Mechanisms
- Immune cells in cancer
Lilly (China)
2015-2017
Eli Lilly (United Kingdom)
2015
Research Triangle Park Foundation
2013
Eli Lilly (United States)
2013
New York University
2004-2011
GlaxoSmithKline (United Kingdom)
2011
University of Oxford
2011
University of California, Los Angeles
2011
Icahn School of Medicine at Mount Sinai
2001-2004
University of California, San Diego
2004
Mouse aortic smooth muscle cells (SMCs) were loaded for 72 h with cholesterol by using cholesterol:methyl-beta-cyclodextrin complexes, leading to approximately 2-fold and 10-fold increases in the contents of total cholesteryl ester, respectively. Foam-cell formation was demonstrated accumulation intracellular, Oil Red O-stained lipid droplets. Immunostaining showed decreased protein levels alpha-actin alpha-tropomyosin increased macrophage markers CD68 Mac-2 antigen. Quantitative real-time...
HDL cholesterol (HDL-C) plasma levels are inversely related to cardiovascular disease risk. Previous studies have shown in animals and humans that promotes regression of atherosclerosis. We hypothesized this was an ability promote the loss monocyte-derived cells (CD68(+), primarily macrophages macrophage foam cells) from plaques. To test hypothesis, we used established model atherosclerosis which plaque-bearing aortic arches apolipoprotein E-deficient (apoE(-/-)) mice (low HDL-C, high...
Background— We previously showed that the progression of atherosclerosis in Reversa mouse ( Ldlr −/− Apob 100/100 Mttp fl/fl Mx1 Cre +/+ ) was arrested when hyperlipidemia normalized by inactivating gene for microsomal triglyceride transfer protein. Here, we tested whether would regress if lipid levels were reduced after advanced plaques formed. Methods and Results— mice fed an atherogenic diet 16 weeks. Plasma then reduced. Within 2 weeks, this reduction led to decreased monocyte-derived...
Background HDL cholesterol levels are inversely correlated with coronary heart disease risk in humans, and animal studies, elevation decreases formation progression of foam-cell lesions. The potential for to affect preexisting advanced atherosclerotic lesions is not known. To approach this issue, we used a novel mouse aortic transplantation model. Methods Results ApoE-deficient (EKO) mice were fed Western-type diet 6 months, thoracic segments containing replaced the abdominal aorta...
LDL receptor-deficient "apolipoprotein (apo)-B100-only" mice (Ldlr-/-Apob100/100 have elevated cholesterol levels on a chow diet and develop severe aortic atherosclerosis. We hypothesized that both the hypercholesterolemia susceptibility to atherosclerosis could be eliminated by switching off hepatic lipoprotein production.We bred Ldlr-/-Apob100/100 were homozygous for conditional allele Mttp (the gene microsomal triglyceride transfer protein) inducible Mx1-Cre transgene. In these animals,...
Protective properties of high-density lipoproteins (HDL) may include reverse cholesterol transport and suppression oxidation inflammation. These were investigated in vivo, as the effects HDL on characteristics atherosclerotic lesions.Male apolipoprotein E knockout (apoE-/-) apoE-/- mice expressing human AI (hAI/apoE-/-) studied up to 20 weeks after commencing a high-fat diet. Plasma was twice high hAI/apoE-/- mice. Over time, aortic root lesion area remained less mice, although plaques...
There has been growing recognition of the essential roles citrate in biomechanical properties mineralized tissues, including teeth and bone. However, sources these tissues have not well defined, contribution to regulation odontogenesis osteogenesis examined. Here, tooth bone phenotypes were examined sodium-dependent transporter (NaCT) Slc13a5 deficient C57BL/6 mice at 13 32 weeks age. deficiency led defective development, characterized by absence mature enamel, formation aberrant enamel...
Objective— Monocyte chemoattractant protein (MCP)-1 is a proatherogenic factor that responsible for ≈60% of plaque macrophages in mouse models atherosclerosis. We investigated whether lysophosphatidylcholine (LPC), enriched oxidized low density lipoprotein, can modulate the expression MCP-1 arterial wall cells. Methods and Results— LPC induced 3-fold increase mRNA rat vascular smooth muscle cells (VSMCs) time- dose-dependent manner. Nuclear runon analysis showed this was attributable to...
Abstract —Cholesterol oxidation products (ChOx) have been reported to cause acute vascular injury in vivo; however, the pharmacokinetics of ChOx after administration and mechanisms by which they chronic are not well understood. To further study atherogenic properties ChOx, New Zealand White rabbits were injected intravenously (70 mg per injection, 20 injections animal) with a mixture having composition similar that found vivo during 70-day period. Total concentrations plasma peaked almost...
Abstract —Circulating cholesterol oxidation products (ChOx) have long been implicated in the etiology of early atherosclerosis; however, direct vivo evidence elucidating their role atherogenesis is only recently becoming available. This study investigated ChOx effects on vascular lesion formation New Zealand White rabbits under controlled hypercholesterolemic conditions. By closely monitoring plasma levels and adjusting dietary intake during a 78-day period, total exposures (cumulative over...
Studies in vitro and vivo of macrophage foam cells have shown evidence cytotoxicity after acyl-CoA:cholesterol acyltransferase (ACAT) inhibition. Foam smooth muscle origin are also found human animal atherosclerotic lesions.To study whether from ACAT inhibition is independent cell type, we first established a protocol to conveniently induce aortic formation using cholesterol-cyclodextrin complexes (CCC). Rat (ASMCs) treated for 48 hours with CCC (20 microg/mL) became by morphological...
Abstract Purpose To test the ability of serial, in vivo magnetic resonance microscopy (MRM) to detect development atherosclerosis and quantify its progression apolipoprotein E‐deficient mice. Materials Methods The abdominal aortae six ApoE −/− three wild‐type (WT) control mice were imaged by MRM at 9.4T. Proton density weighted images obtained (TR = 2000, TE 9 msec) using four signal averages. image resolution was 109 × 500 μm 3 . underwent serial five times over a period ≤ 44 weeks....
The citric acid cycle intermediate citrate plays a crucial role in metabolic processes such as fatty synthesis, glucose metabolism, and <i>β</i>-oxidation. Citrate is imported from the circulation across plasma membrane into liver cells mainly by sodium-dependent transporter (NaCT; SLC13A5). Deletion of NaCT mice led to changes similar caloric restriction; therefore, has been proposed an attractive therapeutic target for treatment obesity type 2 diabetes. In this study, we expressed mouse...