High glucose condition limited the angiogenic/cardiogenic capacity of murine cardiac progenitor cells in in vitro and in vivo milieu

Murine c-kit(+) cardiac cells were isolated and enriched by magnetic activated cell sorting technique. c-kit(+) cells viability and colony-forming activity were evaluated by MTT and clonogenic assay. c-kit(+) cells were exposed to endothelial, pericyte, and cardiomyocyte induction media containing 30mM glucose for 7days. We monitored the level of endothelial (VE-cadherin, CD31, and vWF), pericyte (NG(2), -SMA, and PDGFR-), and cardiomyocyte markers (cTnT) using flow cytometry, real-time Polymerase Chain Reaction (PCR), and Enzyme-Linked Immunosorbent Assay (ELISA) analyses. Ultrastructural changes were studied by transmission electron microscopy (TEM) in cells treated with 5-Azacytidine and 30mM glucose. Matrigel plug assay was performed to determine the angio/cardiogenic property of c-kit(+) cells in a diabetic mouse model. Glucose of 30mM decreased c-kit(+) cells viability and clonogenicity (P<0.05). The transdifferentiation capacity of c-kit(+) cells into the endothelial lineage, pericytes, and cardiomyocytes were reduced through the inhibition of related genes (P<0.05). TEM analysis revealed cardiomyocyte differentiation rate in c-kit(+) cells coincided with an increased intracellular lipid accumulation and reduced number of mitochondria. Similar to in vitro condition, the angiogenic capacity of c-kit(+) cells was aborted in vivo indicated by reduced NG(2), -SMA, CD31, and vWF levels. High glucose condition reduces the angio/cardiogenic capacity of cardiac c-kit(+) cells in vitro and in vivo. Significance of the studyHigh glucose condition seen in diabetes mellitus could affect the regenerative potential of cardiac tissue. The current experiment showed that the exposure of murine cardiac progenitor cells (CD117(+) cells) to condition containing 30mM glucose could decrease the differentiation properties into endothelial cells, pericytes, and mature cardiomyocytes in vitro and in vivo. Our finding confirmed that the angiogenic/cardiogenic potential cardiac progenitor cells decrease under treatment with high glucose content as seen in the diabetic condition.