http://purl.uniprot.org/citations/25278290 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/25278290 | http://www.w3.org/2000/01/rdf-schema#comment | "ObjectiveAtherosclerosis is the primary driver of cardiovascular disease, the leading cause of death worldwide. Identification of naturally occurring atheroprotective genes has become a major goal for the development of interventions that will limit atheroma progression and associated adverse events. To this end, we have identified small proline-rich repeat protein (SPRR3) as selectively upregulated in vascular smooth muscle cells (VSMCs) of atheroma-bearing arterial tissue versus healthy arterial tissue. In this study, we sought to determine the role of SPRR3 in atheroma pathophysiology.Approach and resultsWe found that atheroprone apolipoprotein E-null mice lacking SPRR3 developed significantly greater atheroma burden. To determine the cellular driver(s) of this increase, we evaluated SPRR3-dependent changes in bone marrow-derived cells, endothelial cells, and VSMCs. Bone marrow transplant of SPRR3-expressing cells into SPRR3(-/-)apolipoprotein E-deficient recipients failed to rescue atheroma burden. Similarly, endothelial cells did not exhibit a response to SPRR3 loss. However, atheromas from SPRR3-deficient mice exhibited increased TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive VSMCs compared with control. Cell death in SPRR3-deficient VSMCs was significantly increased in vitro. Conversely, SPRR3-overexpressing VSMCs exhibited reduced apoptosis compared with control. We also observed a PI3K (phosphatidylinositol 3-kinase)/Akt-dependent positive association between SPRR3 expression and levels of active Akt in VSMCs. The survival advantage seen in SPRR3-overexpressing VSMCs was abrogated after the addition of a PI3K/Akt pathway inhibitor.ConclusionsThese results indicate that SPRR3 protects the lesion from VSMC loss by promoting survival signaling in plaque VSMCs, thereby significantly decreasing atherosclerosis progression. As the first identified atheroma-specific VSMC prosurvival factor, SPRR3 represents a potential target for lesion-specific modulation of VSMC survival."xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.org/dc/terms/identifier | "doi:10.1161/atvbaha.114.303644"xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/author | "Li B."xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/author | "Fazio S."xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/author | "Jat P."xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/author | "Atkinson J.B."xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/author | "Linton M.F."xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/author | "Babaev V.R."xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/author | "Young P.P."xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/author | "Pyle A.L."xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/author | "Segedy A.K."xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/name | "Arterioscler Thromb Vasc Biol"xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/pages | "2527-2536"xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/title | "Identification of small proline-rich repeat protein 3 as a novel atheroprotective factor that promotes adaptive Akt signaling in vascular smooth muscle cells."xsd:string |
http://purl.uniprot.org/citations/25278290 | http://purl.uniprot.org/core/volume | "34"xsd:string |
http://purl.uniprot.org/citations/25278290 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25278290 |
http://purl.uniprot.org/citations/25278290 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/25278290 |
http://purl.uniprot.org/uniprot/#_A0A1B0GX15-mappedCitation-25278290 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25278290 |
http://purl.uniprot.org/uniprot/#_G3UWN5-mappedCitation-25278290 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25278290 |
http://purl.uniprot.org/uniprot/#_G3UWW2-mappedCitation-25278290 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25278290 |
http://purl.uniprot.org/uniprot/#_G3UZM8-mappedCitation-25278290 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25278290 |
http://purl.uniprot.org/uniprot/#_O09116-mappedCitation-25278290 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/25278290 |