hydroxysafflor-yellow-a and Myocardial-Ischemia

Hydroxysafflor Yellow A (HSYA), a most representative ingredient of Carthamus tinctorius L., had long been used in treating ischaemic cardiovascular diseases in China and exhibited prominently anticoagulant and pro-angiogenic activities, but the underlying mechanisms remained largely unknown. This study aimed to further elucidate the pro-angiogenic effect and mechanism of HSYA on ischaemic cardiac dysfunction. A C57 mouse model of acute myocardial infarction (AMI) was firstly established, and 25 mg/kg HSYA was intraperitoneally injected immediately after operation and given once, respectively, each morning and evening for 2 weeks. It was found that HSYA significantly improved ischaemia-induced cardiac haemodynamics, enhanced the survival rate, alleviated the myocardial injury and increased the expressions of CD31, vascular endothelial growth factor-A (VEGF-A) and nucleolin in the ischaemic myocardium. In addition, HSYA promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs), enhanced the expressions of nucleolin, VEGF-A and matrix metalloproteinase-9 (MMP-9) in a dose- and time-dependent manner. However, down-regulation of nucleolin expression sharply abrogated the effect mentioned above of HSYA. Further protein-RNA coimmunoprecipitation and immunoprecipitation-RT-PCR assay showed that nucleolin binded to VEGF-A and MMP-9 mRNA and overexpression of nucleolin up-regulated the mRNA expressions of VEGF-A and MMP-9 in the HUVECs through enhancing the stability of VEGF-A and MMP-9 mRNA. Furthermore, HSYA increased the mRNA expressions of VEGF-A and MMP-9 in the extract of antinucleolin antibody-precipitated protein from the heart of AMI mice. Our data revealed that nucleolin mediated the pro-angiogenic effect of HSYA through post-transcriptional regulation of VEGF-A and MMP-9 expression, which contributed to the protective effect of HSYA on ischaemic cardiac dysfunction.

Topics: Animals; Cell Movement; Chalcone; Gene Expression Regulation; Hemodynamics; Human Umbilical Vein Endothelial Cells; Humans; Male; Matrix Metalloproteinase 9; Mice, Inbred C57BL; Myocardial Ischemia; Myocardium; Neovascularization, Physiologic; Nucleolin; Phosphoproteins; Protein Binding; Quinones; RNA Stability; RNA-Binding Proteins; RNA, Messenger; Survival Analysis; Up-Regulation; Vascular Endothelial Growth Factor A

Topics: Chalcone; Gene Expression Regulation, Enzymologic; Heme Oxygenase-1; Humans; Myocardial Ischemia; Myocardial Reperfusion Injury; Quinones; Up-Regulation