Plasma levels of tumor necrosis factor-α and interleukin-6 are associated with diastolic heart failure through downregulation of sarcoplasmic reticulum Ca2+ ATPase

• DOI: 10.1097/ccm.0b013e31820a91b9
• Publication Date: 2011-01-25T06:11:21Z
• Authors: Cho-Kai Wu; Jen-Kuang Lee; Fu-Tien Chiang; Chic-Hsin Yang; Shui-Wei Huang; Juey-Jen Hwang; Jiunn-Lee Lin; Chuen-Den Tseng; Jin-Jer Chen; Chia-Ti Tsai
• Keywords: Phospholamban; Diastolic heart failure

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 association among cytokines (tumor necrosis factor-α and interleukin-6), heart failure, possible molecular mechanism. Design: Prospective case-controlled cohort studies. Setting: University hospital research laboratory. Subjects: Patients a diagnosis failure by echocardiography matched control subjects from general population (study group 1) also intensive care unit 2). Sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene expression calcium decay in HL-1 cardiomyocytes were used as phenotypes failure. Interventions: Soluble plasma levels tumor interleukin-6 measured all subjects. An approximate 1.75-kb promoter SERCA2 was cloned pGL3 luciferase reporter. effect on investigated. Measurements Main Results: had significantly higher than Significant correlations (p < .01 each) found E/Em (r = .87) E/A −0.69), .80) −0.65). Cytokine correlated function patients 2), improved decrease cytokines. Tumor factor-α, interleukin-6, sera downregulated gene. delayed reuptake cardiomyocytes. Conclusions: Through downregulation expression, may cause dysfunction decreasing reuptake. Our study suggest novel therapeutic strategies modulating reactions.