Masami Shimizu‐Albergine

Macrophage TREM2 is a triglyceride-rich lipoprotein receptor that undergoes shedding in prediabetic hepatic steatosis

Jingjing Tang, Jenny E. Kanter, Baohai Shao, Masami Shimizu‐Albergine et autres

Prediabetes associates with increased production of triglyceride-rich lipoproteins (TRLs), cardiovascular disease (CVD), and hepatic steatosis, which is linked to increased plasma levels of soluble TREM2 (sTREM2), the shed domain of TREM2 (triggering receptor expressed on myeloid cells 2). Whether and how TREM2 …

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Abstract Fri102: Systemic Insulin Resistance Causes Inflammatory Activation of Arterial Smooth Muscle Cell Populations in a Mouse Model of Atherosclerosis

Huaqing Zheng, AHREUM KHANG, Masami Shimizu‐Albergine, Baohai Shao et autres

Systemic insulin resistance (IR), a hallmark of prediabetes and type 2 diabetes, accelerates atherosclerotic cardiovascular disease; however, how systemic IR reshapes arterial smooth muscle cell (SMC) phenotypes within lesions remains unclear. We tested the hypothesis that systemic IR reprograms distinct arterial SMC …

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Abstract Or116: Macrophage full-length TREM2 suppresses hepatic apolipoprotein C3 secretion and atherosclerosis in prediabetic hepatic steatosis

Jingjing Tang, Jenny Kanter, Baohai Shao, Masami Shimizu‐Albergine et autres

Prediabetes associates with hepatic steatosis, increased plasma triglyceride-rich lipoproteins (TRLs), and cardiovascular disease (CVD). Hepatic steatosis is linked to increased plasma levels of soluble TREM2 (sTREM2), the shed domain of TREM2. TREM2 is a macrophage receptor mediating lipid uptake and efferocytosis. The …

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Elevated apolipoprotein C3 heightens atherosclerosis risk by mediating arterial accumulation of free cholesterol and local inflammation in diabetes

Karin Bornfeldt, Jenny E. Kanter, Cheng-Chieh Hsu, Farah Kramer et autres

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Abstract We0024: Hepatic Insulin Receptors Have Divergent Effects on Apolipoprotein C3 Production and Atherogenesis in LDL Receptor-silenced Mice

Ah Reum Khang, Masami Shimizu‐Albergine, Baohai Shao, Jingjing Tang et autres

Elevated serum apolipoprotein C3 (APOC3) predicts cardiovascular disease risk in individuals with diabetes. APOC3 slows the clearance of atherogenic triglyceride-rich lipoproteins (TRLs) and their remnants (RLPs). We assessed the hypothesis that hepatic insulin receptor (IR) deficiency causes increased APOC3 levels, altered lipid …

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Type I IFN induces long-chain acyl-CoA synthetase 1 to generate a phosphatidic acid reservoir for lipotoxic saturated fatty acids

Shelley Barnhart, Masami Shimizu‐Albergine, Eyal Kedar, Vishal M Kothari et autres

Long-chain acyl-CoA synthetase 1 (ACSL1) catalyzes the conversion of long-chain fatty acids to acyl-CoAs. ACSL1 is required for β-oxidation in tissues that rely on fatty acids as fuel, but no consensus exists on why ACSL1 is induced by inflammatory mediators in immune …

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Imbalance of APOB Lipoproteins and Large HDL in Type 1 Diabetes Drives Atherosclerosis

Vishal M Kothari, Tse Wing Winnie Ho, Ainara Gonzalez Cabodevilla, Yi He et autres

BACKGROUND: Individuals with type 1 diabetes (T1D) generally have normal or even higher HDL (high-density lipoprotein)-cholesterol levels than people without diabetes yet are at increased risk for atherosclerotic cardiovascular disease (CVD). Human HDL is a complex mixture of particles that can vary …

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A targeted proteomics method for quantifying plasma apolipoprotein kinetics in individual mice using stable isotope labeling

Baohai Shao, Masami Shimizu‐Albergine, Farah Kramer, Jenny E. Kanter et autres

Altered apolipoprotein kinetics play a critical role in promoting dyslipidemia and atherogenesis. Human apolipoprotein kinetics have been extensively evaluated, but similar studies in mice are hampered by the lack of robust methods suitable for the small amounts of blood that can be …

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Abstract 152: Myeloid Cell ADAM17 Impairs Hepatic Triglyceride-Rich Lipoprotein Clearance in an LDL Receptor-Deficient Mouse Model of Prediabetes

Jingjing Tang, Vishal M Kothari, Tomáš Vaisar, Masami Shimizu‐Albergine et autres

ADAM17 (A Disintegrin-like And Metalloproteinase 17) is a transmembrane protease that cleaves its substrates at the cell surface. Cell type-specific substrates cleaved by ADAM17, such as TNFα, can function locally and systemically. When fed a diet enriched in saturated fat, sucrose, and …

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Phosphoproteomic Analysis as an Approach for Understanding Molecular Mechanisms of cAMP-Dependent Actions

Joseph A. Beavo, Martin G. Golkowski, Masami Shimizu‐Albergine, Michael-Claude G. Beltejar et autres

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Kinobead/LC-MS Phosphokinome Profiling Enables Rapid Analyses of Kinase-Dependent Cell Signaling Networks

Martin G. Golkowski, Ho-Tak Lau, Anna Shoemaker, Masami Shimizu‐Albergine et autres

Kinase-catalyzed protein phosphorylation is fundamental to eukaryotic signal transduction, regulating most cellular processes. Kinases are frequently dysregulated in cancer, inflammation, and degenerative diseases, and because they can be inhibited with small molecules, they became important drug targets. Accordingly, analytical approaches that determine …

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TNF-α induces acyl-CoA synthetase 3 to promote lipid droplet formation in human endothelial cells

Hye Seung Jung, Masami Shimizu‐Albergine, Xia Shen, Farah Kramer et autres

Chronic inflammation contributes to cardiovascular disease. Increased levels of the inflammatory cytokine, TNF-α, are often present in conditions associated with cardiovascular disease risk, and TNF-α induces a number of pro-atherogenic effects in macrovascular endothelial cells, including expression of adhesion molecules and chemokines, …

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