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  • 1
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    LRP: role in vascular wall integrity and protection from atherosclerosis (2003)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2003-04-12
    Description: Vascular smooth muscle cell (SMC) proliferation and migration are important events in the development of atherosclerosis. The low-density lipoprotein receptor-related protein (LRP1) mediates suppression of SMC migration induced by platelet-derived growth factor (PDGF). Here we show that LRP1 forms a complex with the PDGF receptor (PDGFR). Inactivation of LRP1 in vascular SMCs of mice causes PDGFR overexpression and abnormal activation of PDGFR signaling, resulting in disruption of the elastic layer, SMC proliferation, aneurysm formation, and marked susceptibility to cholesterol-induced atherosclerosis. The development of these abnormalities was reduced by treatment with Gleevec, an inhibitor of PDGF signaling. Thus, LRP1 has a pivotal role in protecting vascular wall integrity and preventing atherosclerosis by controlling PDGFR activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boucher, Philippe -- Gotthardt, Michael -- Li, Wei-Ping -- Anderson, Richard G W -- Herz, Joachim -- GM 52016/GM/NIGMS NIH HHS/ -- HL20948/HL/NHLBI NIH HHS/ -- HL63762/HL/NHLBI NIH HHS/ -- NS43408/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2003 Apr 11;300(5617):329-32.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9046, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12690199" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Aorta/cytology/metabolism/*pathology ; Arteriosclerosis/*pathology/physiopathology/*prevention & control ; Benzamides ; Cattle ; Cell Division ; Cell Line ; Cholesterol, Dietary/administration & dosage ; Diet, Atherogenic ; Elastin/analysis ; Enzyme Inhibitors/pharmacology ; Imatinib Mesylate ; Ligands ; Low Density Lipoprotein Receptor-Related ; Protein-1/genetics/metabolism/*physiology ; Mesenteric Arteries/cytology/pathology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Muscle, Smooth, Vascular/cytology/*metabolism/pathology ; Myocytes, Smooth Muscle/*metabolism/physiology ; Phosphorylation ; Piperazines/pharmacology ; Platelet-Derived Growth Factor/metabolism/pharmacology ; Proto-Oncogene Proteins c-sis ; Pyrimidines/pharmacology ; Receptor, Platelet-Derived Growth Factor beta/metabolism ; Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Suppression of aging in mice by the hormone Klotho (2005)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2005-08-27
    Description: A defect in Klotho gene expression in mice accelerates the degeneration of multiple age-sensitive traits. Here, we show that overexpression of Klotho in mice extends life span. Klotho protein functions as a circulating hormone that binds to a cell-surface receptor and represses intracellular signals of insulin and insulin-like growth factor 1 (IGF1), an evolutionarily conserved mechanism for extending life span. Alleviation of aging-like phenotypes in Klotho-deficient mice was observed by perturbing insulin and IGF1 signaling, suggesting that Klotho-mediated inhibition of insulin and IGF1 signaling contributes to its anti-aging properties. Klotho protein may function as an anti-aging hormone in mammals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2536606/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2536606/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kurosu, Hiroshi -- Yamamoto, Masaya -- Clark, Jeremy D -- Pastor, Johanne V -- Nandi, Animesh -- Gurnani, Prem -- McGuinness, Owen P -- Chikuda, Hirotaka -- Yamaguchi, Masayuki -- Kawaguchi, Hiroshi -- Shimomura, Iichiro -- Takayama, Yoshiharu -- Herz, Joachim -- Kahn, C Ronald -- Rosenblatt, Kevin P -- Kuro-o, Makoto -- R01 AG019712/AG/NIA NIH HHS/ -- R01 AG019712-05/AG/NIA NIH HHS/ -- R01 AG025326/AG/NIA NIH HHS/ -- R01 AG025326-03/AG/NIA NIH HHS/ -- R01AG19712/AG/NIA NIH HHS/ -- R01AG25326/AG/NIA NIH HHS/ -- R37 HL063762/HL/NHLBI NIH HHS/ -- U24 DK059637/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2005 Sep 16;309(5742):1829-33. Epub 2005 Aug 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, University of Texas (UT) Southwestern Medical Center at Dallas, 5323 Harry Hines Bouleuvard, Dallas, TX 75390-9072, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16123266" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/genetics/*physiology ; Animals ; Blood Glucose/analysis ; Cell Line ; Cell Line, Tumor ; Eating ; Female ; Glucuronidase ; Insulin/blood/metabolism ; Insulin Resistance ; Insulin-Like Growth Factor I/metabolism/pharmacology ; Ligands ; Longevity/genetics/*physiology ; Male ; Membrane Proteins/chemistry/*genetics/pharmacology/*physiology ; Mice ; Mice, Transgenic ; Myoblasts/metabolism ; Oxygen Consumption ; Peptide Fragments/chemistry/pharmacology ; Phosphorylation ; Receptor, IGF Type 1/metabolism ; Receptor, Insulin/metabolism ; Receptors, Cell Surface/metabolism ; Recombinant Proteins/chemistry/isolation & purification/metabolism ; Signal Transduction
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
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    PAPER CURRENT
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