A5006709002- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Drug Transport and Resistance Mechanisms
- Cancer, Lipids, and Metabolism
- Lipoproteins and Cardiovascular Health
- Acute Myocardial Infarction Research
- Hormonal Regulation and Hypertension
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Atrial Fibrillation Management and Outcomes
- Hereditary Neurological Disorders
- Blood Coagulation and Thrombosis Mechanisms
- Immune Cell Function and Interaction
- Blood properties and coagulation
- Peripheral Neuropathies and Disorders
- Venous Thromboembolism Diagnosis and Management
- Systemic Lupus Erythematosus Research
- Adipokines, Inflammation, and Metabolic Diseases
- Lipid metabolism and disorders
- Myasthenia Gravis and Thymoma
- Caveolin-1 and cellular processes
- Adipose Tissue and Metabolism
CSL (Japan)
2024
Daiichi-Sankyo (Japan)
2002-2020
Daiichi Sankyo (Germany)
2010
Columbia University
2007-2010
Yale University
2010
Biomedical Research Laboratories (United States)
2003
Osaka University
2002
Dysregulation of adipocyte-derived bioactive molecules plays an important role in the development atherosclerosis. We previously reported that adiponectin, adipocyte-specific plasma protein, accumulated injured artery from and suppressed endothelial inflammatory response vascular smooth muscle cell proliferation, as well macrophage-to-foam transformation vitro. The current study investigated whether increased adiponectin could actually reduce atherosclerosis vivo.Apolipoprotein E-deficient...
HDLs protect against the development of atherosclerosis, but underlying mechanisms are poorly understood. HDL and its apolipoproteins can promote cholesterol efflux from macrophage foam cells via ATP-binding cassette transporters ABCA1 ABCG1. Experiments addressing individual roles ABCG1 in atherosclerosis have produced mixed results, perhaps because compensatory upregulation KO models. To clarify role transporter-mediated sterol this disease process, we transplanted BM Abca1–/–Abcg1–/– mice...
Liver X receptors (LXRα and LXRβ) are nuclear receptors, which important regulators of cholesterol lipid metabolism. LXRs control genes involved in efflux macrophages, bile acid synthesis liver intestinal absorption. also regulate participating lipogenesis. To determine whether the activation LXR promotes or inhibits development atherosclerosis, T‐0901317, a synthetic ligand, was administered to low density lipoprotein receptor (LDLR) −/− mice. T‐0901317 significantly reduced atherosclerotic...
Oxidized sterols consumed in the diet or formed on low-density lipoprotein (LDL) are toxic to endothelial cells and macrophages thought have a central role promoting atherogenesis. The ATP-binding cassette transporter ABCG1 was recently shown promote efflux of cholesterol from high-denisty (HDL). We show that HDL protects apoptosis induced by loading with free oxidized LDL. protective effect reduced Abcg1(-/-) macrophages, especially after Similarly, exerted against 7-ketocholesterol, major...
Plasma HDL levels are inversely related to the incidence of atherosclerotic disease. Some atheroprotective effects likely mediated via preservation EC function. Whether beneficial on ECs depend its involvement in cholesterol efflux ATP-binding cassette transporters ABCA1 and ABCG1, which promote oxysterols from macrophages, has not been investigated. To address this, we assessed endothelial function Abca1–/–, Abcg1–/–, Abca1–/–Abcg1–/– mice fed either a high-cholesterol diet (HCD) or Western...
The KK/San obese and diabetic mouse, a mutant strain from KK mice, exhibits significantly low plasma triglyceride levels. In genetic analysis identified mutation in the gene encoding angiopoietinlike protein 3 (Angptl3), liver-specific secretory protein, which had suppressive effect on lipoprotein lipase activity. current study, LXR ligands augmented Angptl3 mRNA expression production hepatoma cells. LXR.retinoid X receptor (RXR) complex increased promoter activity of gene. Serial deletion...
To investigate whether cholesterol efflux to high-density lipoprotein (HDL) via ATP-binding cassette transporter G1 (ABCG1) modulates the interaction of caveolin (Cav) 1 and endothelial NO synthase (eNOS).ABCG1 promotes 7-oxysterol from cells (ECs) HDL. It was previously reported that ABCG1 protects against dietary cholesterol-induced dysfunction by promoting 7-oxysterols Increased loading in ECs is known cause an inhibitory between Cav-1 eNOS impaired release. In human aortic ECs, free...
Exposure of blood to tissue factor (TF) rapidly initiates the coagulation serine protease cascades. TF is expressed by macrophages and other types cell within atherosclerotic lesions plays an important role in thrombus formation after plaque rupture. Macrophage expression induced pro-inflammatory stimuli including lipopolysaccharide (LPS), interleukin-1beta tumor necrosis factor-alpha. Here we demonstrate that activation liver X receptors (LXRs) LXRalpha LXRbeta suppresses expression....
Enhancement of LCAT (lecithin:cholesterol acyltransferase) activity has possibility to be beneficial for atherosclerosis. To evaluate this concept, we characterized our novel, orally administered, small-molecule activator DS-8190a, which was created from high-throughput screening and subsequent derivatization. We also focused on its mechanism activation the therapeutic with improvement HDL (high-density lipoprotein) functionality. Approach Results: DS-8190a activated human cynomolgus monkey...
Limited data are available regarding the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) in patients experiencing major hemorrhage or requiring expeditious surgical intervention, both globally within Japan. We executed a prospective, observational post-marketing surveillance study receiving 4F-PCC for first time between September 19, 2017 August 15, 2018 Patients were subjected to comprehensive follow-up duration 4 weeks. Of 1381 eligible patients, 1271 (92%)...
We previously conducted a prospective, observational post-marketing surveillance study to assess the safety and effectiveness of four-factor prothrombin complex concentrate (4F-PCC) for rapid vitamin K antagonist (VKA) reversal in Japanese patients. This subgroup analysis compared safety, especially thromboembolic events (TEEs), 4F-PCC by stratifying patients into two subgroups according baseline international normalized ratio (INR) levels with < 2.0 ≥ 2.0. Of 1271 eligible patients, 215...
Abstract Objectives IgPro20, a subcutaneous immunoglobulin replacement therapy, is approved in Japan for chronic inflammatory demyelinating polyneuropathy (CIDP). This post‐marketing surveillance study characterized real‐world treatment patterns and safety profile of injection site reactions associated with IgPro20 Japanese patients CIDP. Methods Patients CIDP initiating between October 2019 September 2022 at medical institutions were followed 6 months. The primary outcome was the incidence...
Oxidized sterols consumed in the diet or formed on low-density lipoprotein (LDL) are toxic to endothelial cells and macrophages thought have a central role promoting atherogenesis. The ATP-binding cassette transporter ABCG1 was recently shown promote efflux of cholesterol from HDL. We show that HDL protects apoptosis induced by loading with free oxidized LDL (oxLDL). protective effect reduced Abcg1 −/− macrophages, especially after LDL. Similarly, exerted against 7-ketocholesterol, major...