| Objective:Recent study revealed that chemokine CC-motif ligand17(CCL17) from dentritic cells could accelerate athrosclerosis through negative regulation on the regulatory T cell homeostasis. The aims of this study were:(1) to investigate the association between serum CCL17level and coronary artery disease (CAD);(2) to explore the association between CCL17level in the peripheral blood mononuclear cell (PBMC) of CAD patients and CAD, and evaluate the influence of oxidized low-density lipoprotein (ox-LDL) and atrovastatin on CCL17level;(3) to examine the role of vorinostat, a specific and potent histone deacetylase inhibitor (HDACi), in the production of CCL17in PBMCs of stable angina pectoris patients.Methods:(1) Eighty-nine CAD patients (30with stable angina pectoris,29with non-ST elevation myocardial infarction and30with ST elevation myocardial infarction) and thirty non-CAD patients were enrolled. Serum CCL17level were determined by enzyme-linked immunosorbent assay (ELISA) before angiography. Severity of coronary artery stenosis was evaluated by Gensini Score.(2) Thirty-six CAD patients (20with stable angina pectoris,16with acute coronary syndrome) and20non-CAD patients were enrolled. PBMCs were isolated from all patients by ficoll-hypaque density gradient centrifugation before angiography and were later co-cultured with10mg/mL ox-LDL,15μmol/L atorvastatin or10mg/mL ox-LDL plus15μmol/L atorvastatin. Then, CCL17level in the supernatant of PBMCs were determined by ELISA.(3) Twenty patients with stable angina pectoris were enrolled. PBMCs were isolated by ficoll-hypaque density gradient centrifugation before angiography and were later co-cultured with different concentrations of vorinostat (0.00～5.00μmol/L). Then, cytotoxicity of vorinostat was examined by Cell Counting Kit-8(CCK-8) and CCL17level in supernatant of PBMCs were determined by ELISA.Results:(1) Patients with CAD have higher serum CCL17level than those without CAD (320.87±148.00pg/mL versus223.20±141.74pg/mL, P=0.002) both before and after adjusting for traditional risk factors. Furthermore, a linear correlation was found between serum CCL17level and the Gensini score (R=0.24, P=0.024).(2) The CCL17level of PBMCs did not differ between CAD and control group. In vitro, ox-LDL increased the production of CCL17in PBMC [CAD group:401.64(297.18,621.41) pg/mL versus312.59(273.96,486.39) pg/mL, P=0.000; control group:445.41(304.97,712.61) pg/mL versus322.62(272.01,411.68) pg/mL,P=0.000], with a particularly enhancing effects in cells from the patients without CAD, and atorvastatin significantly decreased the production of CCL17in PBMCs [CAD group:249.18(206.51,295.48) pg/mL versus312.59(273.96,486.39) pg/mL, P=0.000; control group:250.47(197.74,291.11) pg/mL versus322.62(272.01,411.68) pg/mL, P=0.000].(3)Vorinostat, like other inhibitors of histone deacetylase, exhibits cytotoxic effects in a dose-dependent manner, and also reduced the production of CCL17in vitro (50%reduction at0.2μmol/L).Conclusion:(1) Serum CCL17levels were associated with CAD, independent of traditional cardiovascular risk factors. Also, serum CCL17levels were positively correlated with the severity of coronary artery stenosis. Thus, it could be seen as a biomarker for CAD.(2) Ox-LDL can increase the production of CCL17in PBMC, with particularenhancing effects in cells from the patients without CAD, and atorvastatin significantly decreased the production of CCL17in PBMCs, which means that CCL17might be a new target for the treatment of arthrosclerosis.(3) Vorinostat exhibits anti-inflammatory properties in vitro by reducing CCL17production, which indicates that it may have an anti-athrosclerosis effect. |
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