Shui-Ping Zhao1, Hui-Jun Ye, Hong-Nian Zhou, Sai Nie, Quan-Zhong Li. 1. Department of Cardiology, The Second XiangYa Hospital, Central South University, Middle Renmin Road No. 86, ChangSha, Hunan 410011, People's Republic of China. ZhaoSP@public.cs.hn.cn
Abstract
BACKGROUND: Inflammatory process plays an important role in the pathogenesis of coronary heart disease (CHD). With the growing use of gemfibrozil and other fibrates, their anti-inflammatory effects have been noted. But little is known about the effect of gemfibrozil on tumor necrosis factor (TNF)-alpha secretion in peripheral blood mononuclear cells (PBMC) from patients with coronary heart disease. METHODS: PBMC were obtained from CHD patients (n=16) and healthy controls (n=13). PBMC (2x10(6) cells/ml) were cultured in 24-well plates with or without Ang II (10(-8), 10(-7), 10(-6) mol/l), or Ang II (10(-6) mol/l) plus gemfibrozil (10(-6), 10(-5), 10(-4) mol/l). After 24-h incubation, the supernatants were separated, and TNF-alpha was measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Spontaneous release of TNF-alpha was 299.2+/-110.7 pg/ml in PBMC from CHD patients and 179.3+/-78.2 pg/ml in PBMC from control subjects (P<0.05). Incubated with Ang II (10(-8), 10(-7), 10(-6) mol/l), TNF-alpha secretion was 307.7+/-141.8, 318.9+/-135.6, 328.6+/-123.9 pg/ml in PBMC from CHD patients, and 225.3+/-135.4, 224.1+/-141.0,218.7+/-134.8 pg/ml in PBMC from control subjects, respectively. Ang II did not significantly trigger TNF-alpha secretion in both groups. Compared with that incubated with Ang II (10(-6) mol/l) alone, release of TNF-alpha intervened by gemfibrozil (10(-6),10(-5),10(-4) mol/l) decreased to 279.4+/-132.2, 268.0+/-132.7, 226.6+/-102.7 pg/ml in PBMC from CHD patients, and 177.6+/-94.4, 156.1+/-69.4, 105.3+/-52.7 pg/ml in the control group, respectively. Gemfibrozil (10(-5),10(-4) mol/l) significantly inhibited TNF-alpha secretion in both groups (P<0.05). CONCLUSIONS: Our data demonstrated that gemfibrozil reduced release of TNF-alpha in PBMC both from CHD patients and controls. This effect may partially be relevant to the clinical benefits of gemfibrozil in the treatment of dyslipidemia and atherosclerosis.
BACKGROUND: Inflammatory process plays an important role in the pathogenesis of coronary heart disease (CHD). With the growing use of gemfibrozil and other fibrates, their anti-inflammatory effects have been noted. But little is known about the effect of gemfibrozil on tumor necrosis factor (TNF)-alpha secretion in peripheral blood mononuclear cells (PBMC) from patients with coronary heart disease. METHODS: PBMC were obtained from CHD patients (n=16) and healthy controls (n=13). PBMC (2x10(6) cells/ml) were cultured in 24-well plates with or without Ang II (10(-8), 10(-7), 10(-6) mol/l), or Ang II (10(-6) mol/l) plus gemfibrozil (10(-6), 10(-5), 10(-4) mol/l). After 24-h incubation, the supernatants were separated, and TNF-alpha was measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Spontaneous release of TNF-alpha was 299.2+/-110.7 pg/ml in PBMC from CHD patients and 179.3+/-78.2 pg/ml in PBMC from control subjects (P<0.05). Incubated with Ang II (10(-8), 10(-7), 10(-6) mol/l), TNF-alpha secretion was 307.7+/-141.8, 318.9+/-135.6, 328.6+/-123.9 pg/ml in PBMC from CHD patients, and 225.3+/-135.4, 224.1+/-141.0,218.7+/-134.8 pg/ml in PBMC from control subjects, respectively. Ang II did not significantly trigger TNF-alpha secretion in both groups. Compared with that incubated with Ang II (10(-6) mol/l) alone, release of TNF-alpha intervened by gemfibrozil (10(-6),10(-5),10(-4) mol/l) decreased to 279.4+/-132.2, 268.0+/-132.7, 226.6+/-102.7 pg/ml in PBMC from CHD patients, and 177.6+/-94.4, 156.1+/-69.4, 105.3+/-52.7 pg/ml in the control group, respectively. Gemfibrozil (10(-5),10(-4) mol/l) significantly inhibited TNF-alpha secretion in both groups (P<0.05). CONCLUSIONS: Our data demonstrated that gemfibrozil reduced release of TNF-alpha in PBMC both from CHD patients and controls. This effect may partially be relevant to the clinical benefits of gemfibrozil in the treatment of dyslipidemia and atherosclerosis.
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