Angiogenic changes in co-cultures of mast cells and myocardial microvascular endothelial cells under hyperglycemic conditions

Wang,Zhihua; Zhang,Qingyong; Zhu,Wei; Tao,Jianping; Wei,Meng

doi:10.3892/ijmm.2013.1293

Angiogenic changes in co-cultures of mast cells and myocardial microvascular endothelial cells under hyperglycemic conditions

Authors:
- Zhihua Wang
- Qingyong Zhang
- Wei Zhu
- Jianping Tao
- Meng Wei
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Affiliations: Division of Cardiology, Shanghai Jiaotong University Sixth Hospital, Shanghai 200233, P.R. China
Published online on: March 5, 2013 https://doi.org/10.3892/ijmm.2013.1293
Pages: 1177-1185

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Abstract

The aim of the present study was to determine the correlation between angiogenesis and the differential expression of growth factors and their receptors when myocardial microvascular endothelial cells (MMVECs) were co-cultured with mast cell granules (MCGs) under hyperglycemic conditions. MMVECs and mast cells (MCs) were isolated from Wistar rats. An in vitro angiogenesis assay was used to observe any differences when MMVECs were co-cultured with MCGs in normal or hyperglycemic medium. The mRNA and protein expression of growth factors and their receptors were analyzed by real-time reverse transcription (RT)-PCR and western blot analysis. Real-time RT-PCR analysis demonstrated the upregulated mRNA and protein expression of vascular endothelial growth factor (VEGF) in the MMVECs; however, the expression of its receptor, fms-like tyrosine kinase-1 (Flt-1) and fetal liver kinase-1 (Flk‑1), decreased significantly, and the angiogenic ability of the MMVECs decreased under hyperglycemic conditions. The angiogenic ability of the MMVECs cultured under hyperglycemic conditions (even after the addition of MCGs) was inferior to that of the MMVECs cultured under normal glucose conditions. The specific inhibitor of tryptase, N-tosyl-L-lysine chloromethyl ketone (TLCK), suppressed angiogenesis regardless of the glucose concentration, and the specific inhibitor of chymase, N-tosyl-L-phenylalanyl chloromethyl ketone (TPCK), was not as effective as TLCK, which was mainly detected under hyperglycemic conditions. High glucose levels have a profound effect on angiogenesis; this effect may be more pronounced than the effects of MCGs on angiogenesis.

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