The Experts below are selected from a list of 127500 Experts worldwide ranked by ideXlab platform
Sergio Fazio - One of the best experts on this subject based on the ideXlab platform.
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relationship between Low Density Lipoprotein cholesterol and Lipoprotein a Lowering in response to pcsk9 inhibition with evolocumab
Journal of the American Heart Association, 2019Co-Authors: Michael D Shapiro, Ransi Somaratne, Hagai Tavori, Jessica Minnier, Helina Kassahun, Andrea Flower, Sergio FazioAbstract:Background Beyond their potent LDL (Low‐Density Lipoprotein) cholesterol (LDL‐C)–Lowering efficacy (50–60%), PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors also reduce Lp(a) (lipo...
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serum proprotein convertase subtilisin kexin type 9 and cell surface Low Density Lipoprotein receptor evidence for a reciprocal regulation
Circulation, 2013Co-Authors: Hagai Tavori, Daping Fan, John L Blakemore, Patricia G Yancey, Lei Ding, Macrae F Linton, Sergio FazioAbstract:Background—Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulates Low-Density Lipoprotein (LDL) receptor (LDLR) degradation, thus influencing serum cholesterol levels. However, dysfunction...
Hagai Tavori - One of the best experts on this subject based on the ideXlab platform.
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relationship between Low Density Lipoprotein cholesterol and Lipoprotein a Lowering in response to pcsk9 inhibition with evolocumab
Journal of the American Heart Association, 2019Co-Authors: Michael D Shapiro, Ransi Somaratne, Hagai Tavori, Jessica Minnier, Helina Kassahun, Andrea Flower, Sergio FazioAbstract:Background Beyond their potent LDL (Low‐Density Lipoprotein) cholesterol (LDL‐C)–Lowering efficacy (50–60%), PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors also reduce Lp(a) (lipo...
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serum proprotein convertase subtilisin kexin type 9 and cell surface Low Density Lipoprotein receptor evidence for a reciprocal regulation
Circulation, 2013Co-Authors: Hagai Tavori, Daping Fan, John L Blakemore, Patricia G Yancey, Lei Ding, Macrae F Linton, Sergio FazioAbstract:Background—Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulates Low-Density Lipoprotein (LDL) receptor (LDLR) degradation, thus influencing serum cholesterol levels. However, dysfunction...
Philippe Costet - One of the best experts on this subject based on the ideXlab platform.
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fasting induces hyperlipidemia in mice overexpressing proprotein convertase subtilisin kexin type 9 lack of modulation of very Low Density Lipoprotein hepatic output by the Low Density Lipoprotein receptor
Endocrinology, 2006Co-Authors: Gilles Lambert, Maud Chetiveaux, Michel Krempf, Annelaure Jarnoux, Thierry Pineau, Olivier Pape, Christian L Laboisse, Philippe CostetAbstract:Several proprotein convertase subtilisin kexin type 9 (PCSK9) mutations lead to familial hypercholesterolemia by virtue of its role as a negative modulator of the Low-Density Lipoprotein receptor (LDLr). Here, we uncover that upon dietary challenge, the down-regulation of the LDLr is also a key mechanism by which PCSK9 modulates the hepatic production of apoLipoprotein-B-containing Lipoproteins. Thus, adenoviral-mediated overexpression of PCSK9 in 24-h fasted mice results in massive hyperlipidemia, due to a striking increase in very-Low-Density Lipoprotein (VLDL) triglycerides and apoLipoprotein B100 hepatic output. Similar studies in LDLr (−/−) mice demonstrate that PCSK9-mediated alteration of VLDL output in the fasted state requires the LDLr. This increased production of VLDL was associated with a concomitant reduction of intrahepatic lipid stores as well as a lack of down-regulation of peroxisome proliferator-activated receptor-α activity and target genes expression. Finally, we show that PCSK9 hepati...
Tokuo Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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structure chromosome location and expression of the human very Low Density Lipoprotein receptor gene
Journal of Biological Chemistry, 1994Co-Authors: Juro Sakai, Sadao Takahashi, Yutaka Kawarabayasi, Atsushi Hoshino, Yukio Miura, Hirofumi Ishii, Hiroyuki Suzuki, Tokuo YamamotoAbstract:Isolation and characterization of cDNAs encoding human very Low Density Lipoprotein (VLDL) receptor revealed the presence of two forms of the receptor: one consists of five domains that resemble the Low Density Lipoprotein (LDL) receptor, and a variant form lacks an O-linked sugar domain. More than 96% of amino acids in the human and rabbit VLDL receptors are identical, whereas those in the LDL receptors are less conserved between the two species (76%). The human VLDL receptor gene contains 19 exons spanning approximately 40 kilobases. The exon-intron organization of the gene is almost the same as that of the LDL receptor gene, except for an extra exon that encodes an additional repeat in the ligand binding domain of the VLDL receptor. Analysis of DNA from human-rodent hybrid cells revealed that the gene is located on chromosome 9. Although the 5'-flanking region of the VLDL receptor gene contains two copies of a sterol regulatory element-1 like sequence, the levels of mRNA for the receptor in THP-1 human monocytic leukemia cells were unchanged by sterols. The 5'-untranslated region of the receptor mRNA contains a polymorphic triplet repeat found also in the fragile X syndrome gene.
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rabbit very Low Density Lipoprotein receptor a Low Density Lipoprotein receptor like protein with distinct ligand specificity
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: Sadao Takahashi, Yutaka Kawarabayasi, Tsuguhiko Nakai, Juro Sakai, Tokuo YamamotoAbstract:Abstract A cDNA that expresses a receptor for very Low Density Lipoprotein (VLDL) was isolated from a rabbit heart cDNA library and characterized. The deduced amino acid sequence of the cDNA revealed that the cDNA encodes a protein with striking homology to the Low Density Lipoprotein (LDL) receptor. Like the LDL receptor, the mature protein consists of the folLowing five domains spanning 846 amino acids: 328 N-terminal amino acids including an 8-fold repeat of 40 amino acids homologous to the ligand binding repeat of the LDL receptor; 396 amino acid residues homologous to the epidermal growth factor precursor including three cysteine-rich repeats; a region immediately outside of the plasma membrane rich in serines and threonines; 22 amino acids traversing the plasma membrane; and 54 amino acids including the NPVY sequence that is required for clustering of the LDL receptor in coated pits and that projects into the cytoplasm. LDL-receptor-deficient Chinese hamster ovary cells transfected with the cDNA bound and internalized VLDL, beta-migrating VLDL, and intermediate Density Lipoprotein but did not bind LDL with high affinity. The 3.6- and 9.5-kilobase mRNAs for the VLDL receptor are highly abundant in heart, muscle, and adipose tissue. Barely detectable amounts of the mRNAs were present in liver. Based on the structural features, ligand specificity, and tissue expression of the mRNAs, we suggest that this VLDL receptor may mediate uptake of apoLipoprotein E-containing Lipoproteins enriched with triglyceride in nonhepatic tissues that are active in fatty acid metabolism.
Sadao Takahashi - One of the best experts on this subject based on the ideXlab platform.
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Species differences of macrophage very Low-Density-Lipoprotein (VLDL) receptor protein expression
Biochemical and biophysical research communications, 2011Co-Authors: Sadao Takahashi, Takashi Ito, Yasuo Zenimaru, Jinya Suzuki, Isamu Miyamori, Masao Takahashi, Masafumi Takahashi, Takafumi Ishida, Tatsuro Ishida, Ken-ichi HirataAbstract:Triglyceride-rich Lipoproteins (TGRLs) and Low-Density-Lipoprotein (LDL) cholesterol are independent risk factors for coronary artery disease. We have previously proposed that the very Low-Density-Lipoprotein (VLDL) receptor is one of the receptors required for foam cell formation by TGRLs in human macrophages. However, the VLDL receptor proteins have not been detected in atherosclerotic lesions of several animal models. Here we showed no VLDL receptor protein was detected in mouse macrophage cell lines (Raw264.7 and J774.2) or in mouse peritoneal macrophages in vitro. Furthermore, no VLDL receptor protein was detected in macrophages in atherosclerotic lesions of chow-fed apoLipoprotein E-deficient or cholesterol-fed LDL receptor-deficient mice in vivo. In contrast, macrophage VLDL receptor protein was clearly detected in human macrophages in vitro and in atherosclerotic lesions in myocardial infarction-prone Watanabe-heritable hyperlipidemic (WHHLMI) rabbits in vivo. There are species differences in the localization of VLDL receptor protein in vitro and in vivo. Since VLDL receptor is expressed on macrophages in atheromatous plaques of both rabbit and human but not in mouse models, the mechanisms of atherogenesis and/or growth of atherosclerotic lesions in mouse models may be partly different from those of humans and rabbits.
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structure chromosome location and expression of the human very Low Density Lipoprotein receptor gene
Journal of Biological Chemistry, 1994Co-Authors: Juro Sakai, Sadao Takahashi, Yutaka Kawarabayasi, Atsushi Hoshino, Yukio Miura, Hirofumi Ishii, Hiroyuki Suzuki, Tokuo YamamotoAbstract:Isolation and characterization of cDNAs encoding human very Low Density Lipoprotein (VLDL) receptor revealed the presence of two forms of the receptor: one consists of five domains that resemble the Low Density Lipoprotein (LDL) receptor, and a variant form lacks an O-linked sugar domain. More than 96% of amino acids in the human and rabbit VLDL receptors are identical, whereas those in the LDL receptors are less conserved between the two species (76%). The human VLDL receptor gene contains 19 exons spanning approximately 40 kilobases. The exon-intron organization of the gene is almost the same as that of the LDL receptor gene, except for an extra exon that encodes an additional repeat in the ligand binding domain of the VLDL receptor. Analysis of DNA from human-rodent hybrid cells revealed that the gene is located on chromosome 9. Although the 5'-flanking region of the VLDL receptor gene contains two copies of a sterol regulatory element-1 like sequence, the levels of mRNA for the receptor in THP-1 human monocytic leukemia cells were unchanged by sterols. The 5'-untranslated region of the receptor mRNA contains a polymorphic triplet repeat found also in the fragile X syndrome gene.
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rabbit very Low Density Lipoprotein receptor a Low Density Lipoprotein receptor like protein with distinct ligand specificity
Proceedings of the National Academy of Sciences of the United States of America, 1992Co-Authors: Sadao Takahashi, Yutaka Kawarabayasi, Tsuguhiko Nakai, Juro Sakai, Tokuo YamamotoAbstract:Abstract A cDNA that expresses a receptor for very Low Density Lipoprotein (VLDL) was isolated from a rabbit heart cDNA library and characterized. The deduced amino acid sequence of the cDNA revealed that the cDNA encodes a protein with striking homology to the Low Density Lipoprotein (LDL) receptor. Like the LDL receptor, the mature protein consists of the folLowing five domains spanning 846 amino acids: 328 N-terminal amino acids including an 8-fold repeat of 40 amino acids homologous to the ligand binding repeat of the LDL receptor; 396 amino acid residues homologous to the epidermal growth factor precursor including three cysteine-rich repeats; a region immediately outside of the plasma membrane rich in serines and threonines; 22 amino acids traversing the plasma membrane; and 54 amino acids including the NPVY sequence that is required for clustering of the LDL receptor in coated pits and that projects into the cytoplasm. LDL-receptor-deficient Chinese hamster ovary cells transfected with the cDNA bound and internalized VLDL, beta-migrating VLDL, and intermediate Density Lipoprotein but did not bind LDL with high affinity. The 3.6- and 9.5-kilobase mRNAs for the VLDL receptor are highly abundant in heart, muscle, and adipose tissue. Barely detectable amounts of the mRNAs were present in liver. Based on the structural features, ligand specificity, and tissue expression of the mRNAs, we suggest that this VLDL receptor may mediate uptake of apoLipoprotein E-containing Lipoproteins enriched with triglyceride in nonhepatic tissues that are active in fatty acid metabolism.
