The effect of recombinant human interleukin-2 activated natural killer cells on angiogenesis and cardiac function in rats with experimental myocardial infarction.
- Author:
Zhong-hua WANG
1
;
Gang DAI
;
Rong-liang ZHOU
;
Ze-min KUANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Heart; physiology; Humans; Interleukin-2; pharmacology; Killer Cells, Natural; drug effects; physiology; Myocardial Infarction; physiopathology; Neovascularization, Physiologic; Rats; Rats, Sprague-Dawley; Recombinant Proteins; pharmacology
- From: Chinese Journal of Cardiology 2013;41(9):778-784
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effect of recombinant human interleukin-2 (rhIL-2) activated natural killer cells (rhIL-2-NK) on angiogenesis and cardiac function of rats with myocardial infarction (MI).
METHODSNatural killer cells (NKs) were isolated and activated by rhIL-2 in vitro. Untreated NKs were used as the control, the killing capacity of rhIL-2-NK were evaluated with cytotoxicity assay. Cardiac microvascular endothelial cells (CMECs) were cocultured with rhIL-2-NK. One hour after MI, rats were randomly divided into rhIL-2-NK group, NK group and blank control group and NK, rhIL-2-NK and PBS were injected directly in the infracted myocardium. At the 0, 1(st), 3(rd), 5(th), 7(th) and 20(th)th day after MI, the mRNA expression of monocyte chemotactic protein-1 (MCP-1), Tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) were was detected by q-PCR essay. At the end of the therapy, the platelet endothelial cell adhesion molecule-1(CD31) and vascular endothelial growth factor (VEGF) were evaluated through immunohistochemical assay, and the cardiac function observed with echocardiography, homodynamic measurements.
RESULTSThe NKs were isolated successfully and the CMEC were proliferated remarkably by coculturing with rhIL-2-NK (P < 0.01). The mRNA expression of MCP-1, TNF-α, CD31 and rhIL-2, VEGF were significantly upregulated in rhIL-2-NK group than in the PBS control group (P < 0.01). Four weeks after operation, LVEF was significantly higher in rhIL-2-NK group than in the PBS control group [(77.56 ± 15.67)% vs. (41.47 ± 12.21)%, P < 0.05)] and histomorphology assay revealed that the density of microvascular endothelial (MVD) of rhIL-2-NK group was significantly higher than that of PBS control group (17.35 ± 1.82 vs. 4.76 ± 0.92, P < 0.01).
CONCLUSIONSMyocardial injection of rhIL-2-NK could promote angiogenesis and improve cardiac function in MI rats.