Protein kinase D1 (PKD1) promotes angiogenesis following myocardial infarction via vascular endothelial growth factor (VEGF) pathway

This study is to investigate the effects of protein kinase D1 (PKD1) on the angiogenic process following myocardial infarction. Rat model of myocardial infarction was established, and endothelial progenitor cells (EPCs) were isolated from normal rats and cultured in vitro. These animal and cell models were administrated with PKD1, alone or together with its inhibitor. Histological detection was performed with H&E staining, and myocardial ultrastructure was evaluated with TEM. VEGF and KDR expression levels were detected with RT-PCR and Western blot analysis. Histological detection showed irregular tissue arrangement and vague cell outline in the model group, accompanied with nuclear fusion. Significant fibrosis was noted in the necrotic myocardial tissue, with rare clear and complete vessels. TEM indicated that, in the model group, the myocardial tissue was irregularly arranged, with relatively unclear intercalated disk. Intact endothelial cells were rarely seen, with severe shrinkage and significantly reduced volume. All these pathological changes could be dramatically alleviated by the treatment of PKD1, which could also be abolished by its inhibitor CID755673. Results from RT-PCR and Western blot analysis showed that, the treatment of PKD1 significantly elevated the mRNA and protein expression levels of VEGF and KDR in the myocardial tissue in the rat models of myocardial infarction. In addition, in the in vitro EPCs, PKD1 significantly up-regulated the mRNA and protein expression levels of VEGF and KDR. PKD1 could significantly promote the angiogenic process following myocardial infarction, which might be mediated by the VEGF signaling pathway.