Low oxygen tension positively influences cardiomyocyte progenitor cell function.
Bottom Line: After MI, deprivation of oxygen is the first major change in the cardiac environment.Knockdown of TSP-2 resulted in increased proliferation, migration and MMP activity.In conclusion, short exposure to hypoxia increases migratory and invasive capacities of hCMPCs and prolonged exposure induces proliferation, an angiogenic secretion profile and dampens migration, likely controlled by TSP-2.
Affiliation: Department of Molecular Cell Biology and Center for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.Show MeSH
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Mentions: Because repair of ischemic damage of cardiac tissue takes longer than 1 day we also explored the effects of prolonged (6 and 9 days) exposure to hypoxia on the different aspects of migration. Because ECM modulators are important for the migration of (progenitor) cells through cardiac tissue, we determined the effect hypoxia had of MMP-2 and -9, and the MMP inhibitors TIMP and TSP [27, 28]. Using zymography and RT-qPCR we observed that hCMPCs express high levels MMP-2 mRNA and secreted large amounts of MMP-2 protein (Fig. 6A and B). Culturing hCMPCs under hypoxic conditions did not affect the MMP-2 gene expression nor the MMP-2 protein secretion (Fig. 6A and B). MMP-9 protein or mRNA levels were below the detection level in all conditions analysed (data not shown).
Affiliation: Department of Molecular Cell Biology and Center for Biomedical Genetics, Leiden University Medical Center, Leiden, The Netherlands.