Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/27151399http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27151399http://www.w3.org/2000/01/rdf-schema#comment"

Rationale

Intimal calcification is highly correlated with atherosclerotic plaque burden, but the underlying mechanism is poorly understood. We recently reported that cartilage oligomeric matrix protein (COMP), a component of vascular extracellular matrix, is an endogenous inhibitor of vascular smooth muscle cell calcification.

Objective

To investigate whether COMP affects atherosclerotic calcification.

Methods and results

ApoE(-/-)COMP(-/-) mice fed with chow diet for 12 months manifested more extensive atherosclerotic calcification in the innominate arteries than did ApoE(-/-) mice. To investigate which origins of COMP contributed to atherosclerotic calcification, bone marrow transplantation was performed between ApoE(-/-) and ApoE(-/-)COMP(-/-) mice. Enhanced calcification was observed in mice transplanted with ApoE(-/-)COMP(-/-) bone marrow compared with mice transplanted with ApoE(-/-) bone marrow, indicating that bone marrow-derived COMP may play a critical role in atherosclerotic calcification. Furthermore, microarray profiling of wild-type and COMP(-/-) macrophages revealed that COMP-deficient macrophages exerted atherogenic and osteogenic characters. Integrin β3 protein was attenuated in COMP(-/-) macrophages, and overexpression of integrin β3 inhibited the shift of macrophage phenotypes by COMP deficiency. Furthermore, adeno-associated virus 2-integrin β3 infection attenuated atherosclerotic calcification in ApoE(-/-)COMP(-/-) mice. Mechanistically, COMP bound directly to β-tail domain of integrin β3 via its C-terminus, and blocking of the COMP-integrin β3 association by β-tail domain mimicked the COMP deficiency-induced shift in macrophage phenotypes. Similar to COMP deficiency in mice, transduction of adeno-associated virus 2-β-tail domain enhanced atherosclerotic calcification in ApoE(-/-) mice.

Conclusions

These results reveal that COMP deficiency acted via integrin β3 to drive macrophages toward the atherogenic and osteogenic phenotype and thereby aggravate atherosclerotic calcification."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.org/dc/terms/identifier"doi:10.1161/circresaha.115.308021"xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Cui Q."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Gao C."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Fu Y."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Huang Y."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Jia Y."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Li T."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Li Y."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Liang Y."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Ma W."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Wang M."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Xu Q."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Wang X."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Zhu W."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Yu F."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/author"Kong W."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/date"2016"xsd:gYear
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/name"Circ Res"xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/pages"261-276"xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/title"Shift of Macrophage Phenotype Due to Cartilage Oligomeric Matrix Protein Deficiency Drives Atherosclerotic Calcification."xsd:string
http://purl.uniprot.org/citations/27151399http://purl.uniprot.org/core/volume"119"xsd:string
http://purl.uniprot.org/citations/27151399http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/27151399
http://purl.uniprot.org/citations/27151399http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/27151399
▶