https://scholars.lib.ntu.edu.tw/handle/123456789/524281
標題: | Plasma levels of tumor necrosis factor-α and interleukin-6 are associated with diastolic heart failure through downregulation of sarcoplasmic reticulum Ca2+ ATPase | 作者: | CHO-KAI WU JEN-KUANG LEE FU-TIEN CHIANG Yang C.-H. Huang S.-W. HWANG, JUEY-JEN JIUNN-LEE LIN Tseng C.-D. Chen J.-J. CHIA-TI TSAI |
公開日期: | 2011 | 出版社: | Lippincott Williams and Wilkins | 卷: | 39 | 期: | 5 | 起(迄)頁: | 984-992 | 來源出版物: | Critical Care Medicine | 摘要: | OBJECTIVE: The inflammatory process is associated with cardiac diastolic dysfunction, which has been demonstrated to be an independent prognostic marker for the mortality of critically ill patients. We investigated the association among inflammatory cytokines (tumor necrosis factor-α and interleukin-6), diastolic heart failure, and the possible molecular mechanism. DESIGN: Prospective case-controlled cohort and molecular studies. SETTING: University hospital and research laboratory. SUBJECTS: Patients with a diagnosis of diastolic heart failure by echocardiography and matched control subjects from the general population (study group 1) and also subjects from the intensive care unit (study group 2). Sarcoplasmic reticulum Ca-ATPase (SERCA2) gene expression and diastolic calcium decay in HL-1 cardiomyocytes were used as molecular phenotypes of diastolic heart failure. INTERVENTIONS: Soluble plasma levels of tumor necrosis factor-α and interleukin-6 were measured in all subjects. An approximate 1.75-kb promoter of the SERCA2 gene was cloned to the pGL3 luciferase reporter. The effect of tumor necrosis factor-α and interleukin-6 on SERCA2 gene expression and diastolic calcium decay of HL-1 cardiomyocytes were investigated. MEASUREMENTS AND MAIN RESULTS: Patients with diastolic heart failure had significantly higher plasma levels of tumor necrosis factor-α and interleukin-6 than the control subjects. Significant correlations (p <.01 for each) were found for tumor necrosis factor-α and E/Em (r =.87) and E/A (r =-0.69), and for interleukin-6 and E/Em (r =.80) and E/A (r =-0.65). Cytokine levels were also correlated with diastolic function in critically ill patients (study group 2), and diastolic function improved significantly in association with decrease of cytokines. Tumor necrosis factor-α, interleukin-6, and sera from critically ill patients downregulated the expression of the SERCA2 gene. Tumor necrosis factor-α and interleukin-6 also delayed the diastolic calcium reuptake and decay in cardiomyocytes. CONCLUSIONS: Through downregulation of SERCA2 gene expression, inflammatory cytokines may cause cardiac diastolic dysfunction by decreasing diastolic calcium reuptake. Our study may suggest novel therapeutic strategies for diastolic heart failure and critically ill patients by modulating inflammatory reactions. Copyright ? 2011 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-79955469190&doi=10.1097%2fCCM.0b013e31820a91b9&partnerID=40&md5=1e343a55377ad8600acce6941e1864e2 https://scholars.lib.ntu.edu.tw/handle/123456789/524281 |
ISSN: | 0090-3493 | DOI: | 10.1097/CCM.0b013e31820a91b9 | SDG/關鍵字: | adenosine triphosphatase (calcium); interleukin 6; luciferase; tumor necrosis factor alpha; aged; blood level; calcium transport; conference paper; controlled study; critical illness; diastole; diastolic heart failure; disease association; down regulation; echocardiography; female; gene expression; heart muscle cell; human; human cell; intensive care unit; major clinical study; male; molecular cloning; phenotype; priority journal; promoter region; prospective study; sarcoplasmic reticulum; university hospital |
顯示於: | 醫學系 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。