C-reactive protein contributes to tumor necrosis factor alpha production on monocyte in patients with chronic heart failure.

C反应蛋白有助于慢性心力衰竭患者单核细胞产生肿瘤坏死因子α。

• 批准号: 14570699
• 负责人: NAKAGOMI Akihiro
• 金额: $ 2.11万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570699/
• 关键词: TNF-alpha; C-reactive protein; heart failure; Stains; C-reactive protein; 単核球

Plasma levels of tumor necrosis factor (TNF)-α were elevated and were associated with poor outcomes in patients with chronic heart failure (CHF). Transgenic mice overexpressing TNF-α develop dilated cardiomyopathy, therefore, TNF-α may significant roles in the pathogenesis and exacerbation of CHF. C-reactive protein (CRP) levels in plasma were elevated and were predictive of future poor outcomes in patients with CHF, and CRP induces monocyte TNF-α production, therefore, CRP plays pivotal roles in the pathogenesis and exacerbation of CHF. HMG-CoA reductase inhibitors (statins) improve endothelial dysfunction and reduce plasma cytokines levels, therefore, statins may improve cardiac function and prognosis in CHF patients. Peripheral blood mononuclear cells (PBMC) were stimulated with 25 μg/ml CRP from 18 normal subjects and 52 patients with CHF (EF;26%). Monocyte TNF-α production by CRP at, baseline and after treatment was measured by ELISA. Patients were divided into 2 groups according to the presence of statins therapy ; Statins group (n=26) and NO statins group (n=26). In Statins group, EF was improved after treatment, however, EF in NO statins group was unchanged. Monocyte TNF-α production by CRP in Statins group was decreased, however, this cytokine production was unchanged in NO statins group. Statins attenuate monocyte TNF-α production by CRP and improve cardiac function in CHF patients.

慢性心力衰竭患者血浆肿瘤坏死因子-α水平升高，与预后不良有关。过量表达肿瘤坏死因子-α的转基因小鼠发生扩张型心肌病，因此，肿瘤坏死因子-α可能在心力衰竭的发病和加重中起重要作用。慢性心力衰竭患者血浆C-反应蛋白水平升高，提示预后不良，并可诱导单核细胞产生肿瘤坏死因子-α，在心力衰竭的发病和加重中起关键作用。HMG-CoA还原酶抑制剂(他汀类)可改善内皮功能障碍，降低血浆细胞因子水平，因此他汀类药物可能改善CHF患者的心功能和预后。用25μg/mlCRP刺激18例正常人和52例充血性心力衰竭(EF)患者外周血单个核细胞。用双抗体夹心法检测治疗前、治疗前及治疗后C反应蛋白产生的单核细胞肿瘤坏死因子-α。按有无他汀类药物治疗分为他汀类药物组和非他汀类药物组，每组26例。他汀类药物组治疗后EF较治疗前有所改善，而未服用他汀类药物组EF无明显变化。他汀类药物组单核细胞产生的肿瘤坏死因子-α减少，而无他汀类药物组这一细胞因子的产生无明显变化。他汀类药物可减少C反应蛋白诱导的单核细胞肿瘤坏死因子α的产生，改善心衰患者的心功能。