| http://purl.uniprot.org/citations/25680278 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/25680278 | http://www.w3.org/2000/01/rdf-schema#comment | "Chronic renal disease (CRD) accelerates the development of atherosclerosis. The potent protease cathepsin S cleaves elastin and generates bioactive elastin peptides, thus promoting vascular inflammation and calcification. We hypothesized that selective cathepsin S inhibition attenuates atherogenesis in hypercholesterolemic mice with CRD. CRD was induced by 5/6 nephrectomy in high-fat high-cholesterol fed apolipoprotein E-deficient mice. CRD mice received a diet admixed with 6.6 or 60 mg/kg of the potent and selective cathepsin S inhibitor RO5444101 or a control diet. CRD mice had significantly higher plasma levels of osteopontin, osteocalcin, and osteoprotegerin (204%, 148%, and 55%, respectively; P < 0.05), which were inhibited by RO5444101 (60%, 40%, and 36%, respectively; P < 0.05). Near-infrared fluorescence molecular imaging revealed a significant reduction in cathepsin activity in treated mice. RO5444101 decreased osteogenic activity. Histologic assessment in atherosclerotic plaque demonstrated that RO5444101 reduced immunoreactive cathepsin S (P < 0.05), elastin degradation (P = 0.01), plaque size (P = 0.01), macrophage accumulation (P < 0.01), growth differentiation factor-15 (P = 0.0001), and calcification (alkaline phosphatase activity, P < 0.01; osteocalcin, P < 0.05). Furthermore, cathepsin S inhibitor or siRNA significantly decreased expression of growth differentiation factor-15 and monocyte chemotactic protein-1 in a murine macrophage cell line and human primary macrophages. Systemic inhibition of cathepsin S attenuates the progression of atherosclerotic lesions in 5/6 nephrectomized mice, serving as a potential treatment for atherosclerosis in patients with CRD."xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.ajpath.2014.11.026"xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/author | "Zheng C."xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/author | "Aikawa M."xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/author | "Hartmann G."xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/author | "Gruener S."xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/author | "Fingerle J."xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/author | "Libby P."xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/author | "Aikawa E."xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/author | "Haap W."xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/author | "Figueiredo J.L."xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/author | "Aaron J."xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/author | "de Lima Filho J.L."xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/author | "Lax L."xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/name | "Am J Pathol"xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/pages | "1156-1166"xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/title | "Selective cathepsin S inhibition attenuates atherosclerosis in apolipoprotein E-deficient mice with chronic renal disease."xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://purl.uniprot.org/core/volume | "185"xsd:string |
| http://purl.uniprot.org/citations/25680278 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/25680278 |
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