المؤلفون: Hanrui Zhang, Edward E. Morrisey, Sager J. Gosai, Kate Bermingham, Christine C. Hinkle, Muredach P. Reilly, Evanthia E. Pashos, Marina Cuchel, Wenjun Li, John S. Millar, Ruilan Yan, Stella T. Chou, Ying Liu, Jennifer Tabita-Martinez, Chenyi Xue, Amrith Rodrigues, Wenli Yang, Daniel J. Rader, Daniel VanDorn, Rhia Shah, Mingyao Li, Brian D. Gregory

المصدر: Circulation Research. 117:17-28

مصطلحات موضوعية: Adult, Lipopolysaccharides, Male, Genotype, Lipopolysaccharide, Physiology, Phagocytosis, Induced Pluripotent Stem Cells, Molecular Sequence Data, Cell Culture Techniques, Macrophage polarization, Biology, Article, Proinflammatory cytokine, Transcriptome, Interferon-gamma, Mice, Young Adult, chemistry.chemical_compound, Sequence Homology, Nucleic Acid, Animals, Humans, Secretion, RNA, Messenger, Induced pluripotent stem cell, Cells, Cultured, Embryoid Bodies, Tangier Disease, Aged, Inflammation, Mice, Knockout, Base Sequence, Macrophages, Cell Differentiation, Macrophage Activation, Antigens, Differentiation, Cell biology, Cholesterol, Phenotype, chemistry, Immunology, Female, Efflux, Cardiology and Cardiovascular Medicine, Sequence Alignment, ATP Binding Cassette Transporter 1

الوصف: Rationale: An efficient and reproducible source of genotype-specific human macrophages is essential for study of human macrophage biology and related diseases. Objective: To perform integrated functional and transcriptome analyses of human induced pluripotent stem cell–derived macrophages (IPSDMs) and their isogenic human peripheral blood mononuclear cell–derived macrophage (HMDM) counterparts and assess the application of IPSDM in modeling macrophage polarization and Mendelian disease. Methods and Results: We developed an efficient protocol for differentiation of IPSDM, which expressed macrophage-specific markers and took up modified lipoproteins in a similar manner to HMDM. Like HMDM, IPSDM revealed reduction in phagocytosis, increase in cholesterol efflux capacity and characteristic secretion of inflammatory cytokines in response to M1 (lipopolysaccharide+interferon-γ) activation. RNA-Seq revealed that nonpolarized (M0) as well as M1 or M2 (interleukin-4) polarized IPSDM shared transcriptomic profiles with their isogenic HMDM counterparts while also revealing novel markers of macrophage polarization. Relative to IPSDM and HMDM of control individuals, patterns of defective cholesterol efflux to apolipoprotein A-I and high-density lipoprotein-3 were qualitatively and quantitatively similar in IPSDM and HMDM of patients with Tangier disease, an autosomal recessive disorder because of mutations in ATP-binding cassette transporter AI. Tangier disease-IPSDM also revealed novel defects of enhanced proinflammatory response to lipopolysaccharide stimulus. Conclusions: Our protocol-derived IPSDM are comparable with HMDM at phenotypic, functional, and transcriptomic levels. Tangier disease-IPSDM recapitulated hallmark features observed in HMDM and revealed novel inflammatory phenotypes. IPSDMs provide a powerful tool for study of macrophage-specific function in human genetic disorders as well as molecular studies of human macrophage activation and polarization.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0acc90169da44c924681263b248a1987Test
https://doi.org/10.1161/circresaha.117.305860Test

المؤلفون: Jaime García-Prieto, Enrique Jaimovich, Juan Pablo Muñoz, Olle Larsson, Sean M. Davidson, Sergio Lavandero, Mario Chiong, Ivana Bulatovic, Manuel Estrada, Paola Rebellato, Gyorgy Szabadkai, Andrew F. G. Quest, Cristian Ibarra, Karl-Henrik Grinnemo, Per Uhlén, Yingbo Lin, Paola Rocco, Jose Miguel Vicencio

المصدر: Circulation Research. 112:236-245

مصطلحات موضوعية: Adult, Physiology, Biology, Article, Receptor, IGF Type 1, Rats, Sprague-Dawley, Mice, chemistry.chemical_compound, Membrane Microdomains, Sarcolemma, Animals, Humans, Myocyte, Myocytes, Cardiac, Inositol, Calcium Signaling, Phosphatidylinositol, Transcription factor, Cells, Cultured, Cell Nucleus, Endoplasmic reticulum, Rats, Cell biology, Mice, Inbred C57BL, Cytosol, Animals, Newborn, chemistry, Biochemistry, Cardiology and Cardiovascular Medicine, Nuclear localization sequence, Signal Transduction

الوصف: Rationale: The ability of a cell to independently regulate nuclear and cytosolic Ca 2+ signaling is currently attributed to the differential distribution of inositol 1,4,5-trisphosphate receptor channel isoforms in the nucleoplasmic versus the endoplasmic reticulum. In cardiac myocytes, T-tubules confer the necessary compartmentation of Ca 2+ signals, which allows sarcomere contraction in response to plasma membrane depolarization, but whether there is a similar structure tunneling extracellular stimulation to control nuclear Ca 2+ signals locally has not been explored. Objective: To study the role of perinuclear sarcolemma in selective nuclear Ca 2+ signaling. Methods and Results: We report here that insulin-like growth factor 1 triggers a fast and independent nuclear Ca 2+ signal in neonatal rat cardiac myocytes, human embryonic cardiac myocytes, and adult rat cardiac myocytes. This fast and localized response is achieved by activation of insulin-like growth factor 1 receptor signaling complexes present in perinuclear invaginations of the plasma membrane. The perinuclear insulin-like growth factor 1 receptor pool connects extracellular stimulation to local activation of nuclear Ca 2+ signaling and transcriptional upregulation through the perinuclear hydrolysis of phosphatidylinositol 4,5-biphosphate inositol 1,4,5-trisphosphate production, nuclear Ca 2+ release, and activation of the transcription factor myocyte-enhancing factor 2C. Genetically engineered Ca 2+ buffers—parvalbumin—with cytosolic or nuclear localization demonstrated that the nuclear Ca 2+ handling system is physically and functionally segregated from the cytosolic Ca 2+ signaling machinery. Conclusions: These data reveal the existence of an inositol 1,4,5-trisphosphate–dependent nuclear Ca 2+ toolkit located in direct apposition to the cell surface, which allows the local control of rapid and independent activation of nuclear Ca 2+ signaling in response to an extracellular ligand.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8bd2ac8a70a3127f1f34569c8ce637e8Test
https://doi.org/10.1161/circresaha.112.273839Test

المؤلفون: Yoshio Terao, Makoto Ayaori, Emi Yakushiji, Fumitaka Ohsuzu, Harumi Uto-Kondo, Makoto Sasaki, Shunichi Takiguchi, Katsunori Ikewaki, Atsushi Suzuki, Mai Ito, Kazuhiro Nakaya, Masatsune Ogura, Hideki Ozasa, Tetsuya Hisada

المصدر: Circulation research. 106(4)

مصطلحات موضوعية: Male, Time Factors, Physiology, Coronary Disease, Coffee, chemistry.chemical_compound, Feces, Mice, High-density lipoprotein, Genes, Reporter, Macrophage, Bile, ATP Binding Cassette Transporter, Subfamily G, Member 1, Cross-Over Studies, Middle Aged, Scavenger Receptors, Class B, Up-Regulation, Lipoproteins, LDL, Cholesterol, Biochemistry, Liver, Circulatory system, lipids (amino acids, peptides, and proteins), Female, Efflux, Cardiology and Cardiovascular Medicine, Lipoproteins, HDL, ATP Binding Cassette Transporter 1, Adult, medicine.medical_specialty, Coumaric Acids, Biology, Transfection, Article, Cell Line, Beverages, Caffeic Acids, Downregulation and upregulation, Internal medicine, medicine, Animals, Humans, RNA, Messenger, Scavenger receptor, Apolipoprotein A-I, Dose-Response Relationship, Drug, Macrophages, Biological Transport, Mice, Inbred C57BL, Endocrinology, chemistry, ATP-Binding Cassette Transporters

الوصف: Rationale : Association of habitual coffee consumption with coronary heart disease morbidity and mortality has not been established. We hypothesized that coffee may enhance reverse cholesterol transport (RCT) as the antiatherogenic properties of high-density lipoprotein (HDL). Objective : This study was to investigate whether the phenolic acids of coffee and coffee regulates RCT from macrophages in vitro, ex vivo and in vivo. Methods and Results : Caffeic acid and ferulic acid, the major phenolic acids of coffee, enhanced cholesterol efflux from THP-1 macrophages mediated by HDL, but not apoA-I. Furthermore, these phenolic acids increased both the mRNA and protein levels of ATP-binding cassette transporter (ABC)G1 and scavenger receptor class B type I (SR-BI), but not ABCA1. Eight healthy volunteers were recruited for the ex vivo study, and blood samples were taken before and 30 minutes after consumption of coffee or water in a crossover study. The mRNA as well as protein levels of ABCG1, SR-BI, and cholesterol efflux by HDL were increased in the macrophages differentiated under autologous sera obtained after coffee consumption compared to baseline sera. Finally, effects of coffee and phenolic acid on in vivo RCT were assessed by intraperitoneally injecting [ 3 H]cholesterol-labeled acetyl low-density lipoprotein-loaded RAW264.7 cells into mice, then monitoring appearance of 3 H tracer in plasma, liver, and feces. Supporting in vitro and ex vivo data, ferulic acid was found to significantly increase the levels of 3 H tracer in feces. Conclusions : Coffee intake might have an antiatherogenic property by increasing ABCG1 and SR-BI expression and enhancing HDL-mediated cholesterol efflux from the macrophages via its plasma phenolic acids.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0bf3ded45c78694ab9c5108da236b823Test
https://pubmed.ncbi.nlm.nih.gov/20203311Test