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http://purl.uniprot.org/citations/21071708http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21071708http://www.w3.org/2000/01/rdf-schema#comment"

Rationale

Cardiomyocytes switch substrate utilization from fatty acid to glucose under ischemic conditions; however, it is unknown how perturbations in glycolytic enzymes affect cardiac response to ischemia/reperfusion (I/R). Hexokinase (HK)II is a HK isoform that is expressed in the heart and can bind to the mitochondrial outer membrane.

Objective

We sought to define how HKII and its binding to mitochondria play a role in cardiac response and remodeling after I/R.

Methods and results

We first showed that HKII levels and its binding to mitochondria are reduced 2 days after I/R. We then subjected the hearts of wild-type and heterozygote HKII knockout (HKII(+/)⁻) mice to I/R by coronary ligation. At baseline, HKII(+/)⁻ mice have normal cardiac function; however, they display lower systolic function after I/R compared to wild-type animals. The mechanism appears to be through an increase in cardiomyocyte death and fibrosis and a reduction in angiogenesis; the latter is through a decrease in hypoxia-inducible factor-dependent pathway signaling in cardiomyocytes. HKII mitochondrial binding is also critical for cardiomyocyte survival, because its displacement in tissue culture with a synthetic peptide increases cell death. Our results also suggest that HKII may be important for the remodeling of the viable cardiac tissue because its modulation in vitro alters cellular energy levels, O₂ consumption, and contractility.

Conclusions

These results suggest that reduction in HKII levels causes altered remodeling of the heart in I/R by increasing cell death and fibrosis and reducing angiogenesis and that mitochondrial binding is needed for protection of cardiomyocytes."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.org/dc/terms/identifier"doi:10.1161/circresaha.110.223115"xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Ichikawa Y."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Sun L."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Wu R."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Laakso M."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Ardehali H."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Heikkinen S."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Wyatt E."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Hollmann M.W."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Zuurbier C.J."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Eerbeek O."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Smeele K.M."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Jujo K."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Chawla K."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Nagpal V."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/author"Wasserstrom J.A."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/name"Circ Res"xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/pages"60-69"xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/title"Reduction in hexokinase II levels results in decreased cardiac function and altered remodeling after ischemia/reperfusion injury."xsd:string
http://purl.uniprot.org/citations/21071708http://purl.uniprot.org/core/volume"108"xsd:string
http://purl.uniprot.org/citations/21071708http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21071708
http://purl.uniprot.org/citations/21071708http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21071708
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