RGD Reference Report - Oxygen cycling in conjunction with stem cell transplantation induces NOS3 expression leading to attenuation of fibrosis and improved cardiac function. - Rat Genome Database

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Oxygen cycling in conjunction with stem cell transplantation induces NOS3 expression leading to attenuation of fibrosis and improved cardiac function.

Authors: Khan, M  Meduru, S  Gogna, R  Madan, E  Citro, L  Kuppusamy, ML  Sayyid, M  Mostafa, M  Hamlin, RL  Kuppusamy, P 
Citation: Khan M, etal., Cardiovasc Res. 2012 Jan 1;93(1):89-99. doi: 10.1093/cvr/cvr277. Epub 2011 Oct 19.
RGD ID: 7771563
Pubmed: PMID:22012955   (View Abstract at PubMed)
PMCID: PMC3243040   (View Article at PubMed Central)
DOI: DOI:10.1093/cvr/cvr277   (Journal Full-text)

AIMS: Myocardial infarction (MI) is associated with irreversible loss of viable cardiomyocytes. Cell therapy is a potential option to replace the lost cardiomyocytes and restore cardiac function. However, cell therapy is faced with a number of challenges, including survival of the transplanted cells in the infarct region, which is characterized by abundant levels of oxidants and lack of a pro-survival support mechanism. The goal of the present study was to evaluate the effect of supplemental oxygenation on cell engraftment and functional recovery in a rat model. METHODS AND RESULTS: MI was induced in rats by a 60-min occlusion of the coronary artery, followed by restoration of flow. Mesenchymal stem cells (MSCs), isolated from adult rat bone marrow, were transplanted in the MI region. Rats with transplanted MSCs were exposed to hyperbaric oxygen (HBO: 100% O(2), 2 atmospheres absolute) for 90 min, 5 days/week for 4 weeks. The experimental groups were: MI (control), Ox (MI + HBO), MSC (MI + MSC), and MSC + Ox (MI + MSC + HBO). HBO exposure (oxygenation) was started 3 days after induction of MI. MSCs were transplanted 1 week after induction of MI. Echocardiography showed a significant recovery of cardiac function in the MSC + Ox group, when compared with the MI or MSC group. Oxygenation increased the engraftment of MSCs and vascular density in the infarct region. Molecular analysis of infarct tissue showed a four-fold increase in NOS3 expression in the MSC + Ox group compared with the MI group. CONCLUSIONS: The results showed that post-MI exposure of rats to daily cycles of hyperoxygenation (oxygen cycling) improved stem cell engraftment, cardiac function, and increased NOS3 expression.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
myocardial infarction  ISONos3 (Rattus norvegicus)7771563; 7771563 RGD 
myocardial infarction  IDA 7771563 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nos3  (nitric oxide synthase 3)

Genes (Mus musculus)
Nos3  (nitric oxide synthase 3, endothelial cell)

Genes (Homo sapiens)
NOS3  (nitric oxide synthase 3)


Additional Information